immunoconjugates

Summary

Summary: Combinations of diagnostic or therapeutic substances linked with specific immune substances such as IMMUNOGLOBULINS; MONOCLONAL ANTIBODIES; or ANTIGENS. Often the diagnostic or therapeutic substance is a radionuclide. These conjugates are useful tools for specific targeting of DRUGS and RADIOISOTOPES in the CHEMOTHERAPY and RADIOIMMUNOTHERAPY of certain cancers.

Top Publications

  1. ncbi CTLA-4-Ig regulates tryptophan catabolism in vivo
    Ursula Grohmann
    Department of Experimental Medicine, University of Perugia, 06126 Perugia, Italy
    Nat Immunol 3:1097-101. 2002
  2. pmc Identification and functional characterization of human CD4(+)CD25(+) T cells with regulatory properties isolated from peripheral blood
    H Jonuleit
    Department of Dermatology, University of Mainz, D 55101 Mainz, Germany
    J Exp Med 193:1285-94. 2001
  3. ncbi Brentuximab vedotin (SGN-35) for relapsed CD30-positive lymphomas
    Anas Younes
    Department of Lymphoma and Myeloma, University of Texas M D Anderson Cancer Center, Houston, TX 77030, USA
    N Engl J Med 363:1812-21. 2010
  4. ncbi Enhancement of antitumor immunity by CTLA-4 blockade
    D R Leach
    Cancer Research Laboratory, University of California, Berkeley, CA 94720, USA
    Science 271:1734-6. 1996
  5. pmc Efficacy and safety of abatacept or infliximab vs placebo in ATTEST: a phase III, multi-centre, randomised, double-blind, placebo-controlled study in patients with rheumatoid arthritis and an inadequate response to methotrexate
    M Schiff
    Denver Arthritis Clinic, 200 Spruce Street 100, Denver, CO 80230, USA
    Ann Rheum Dis 67:1096-103. 2008
  6. pmc Validation of the 28-joint Disease Activity Score (DAS28) and European League Against Rheumatism response criteria based on C-reactive protein against disease progression in patients with rheumatoid arthritis, and comparison with the DAS28 based on erythr
    G Wells
    Department of Epidemiology and Community Medicine, University of Ottawa, Canada
    Ann Rheum Dis 68:954-60. 2009
  7. pmc Clinical efficacy and safety of abatacept in methotrexate-naive patients with early rheumatoid arthritis and poor prognostic factors
    R Westhovens
    UZ Gasthuisberg, Department of Rheumatology, B 3000 Leuven, Belgium
    Ann Rheum Dis 68:1870-7. 2009
  8. ncbi Brentuximab vedotin (SGN-35) in patients with relapsed or refractory systemic anaplastic large-cell lymphoma: results of a phase II study
    Barbara Pro
    Fox Chase Cancer Center, 333 Cottman Ave, Philadelphia, PA 19111 2497, USA
    J Clin Oncol 30:2190-6. 2012
  9. ncbi Comparative effectiveness and safety of biological treatment options after tumour necrosis factor α inhibitor failure in rheumatoid arthritis: systematic review and indirect pairwise meta-analysis
    Monika Schoels
    2nd Department of Internal Medicine, Hietzing Hospital, Vienna, Austria
    Ann Rheum Dis 71:1303-8. 2012
  10. ncbi Complexities of CD28/B7: CTLA-4 costimulatory pathways in autoimmunity and transplantation
    B Salomon
    The Committee on Immunology, Ben May Institute for Cancer Research and Department of Pathology, University of Chicago, Chicago, Illinois 60637, USA
    Annu Rev Immunol 19:225-52. 2001

Detail Information

Publications321 found, 100 shown here

  1. ncbi CTLA-4-Ig regulates tryptophan catabolism in vivo
    Ursula Grohmann
    Department of Experimental Medicine, University of Perugia, 06126 Perugia, Italy
    Nat Immunol 3:1097-101. 2002
    ..These data suggest that modulation of tryptophan catabolism is a means by which CTLA-4 functions in vivo and that CTLA-4 acts as a ligand for B7 receptor molecules that transduce intracellular signals...
  2. pmc Identification and functional characterization of human CD4(+)CD25(+) T cells with regulatory properties isolated from peripheral blood
    H Jonuleit
    Department of Dermatology, University of Mainz, D 55101 Mainz, Germany
    J Exp Med 193:1285-94. 2001
    ..However, the refractory state of CD4(+)CD25(+) T cells was partially reversible by the addition of IL-2 or IL-4. These data demonstrate that human blood contains a resident T cell population with potent regulatory properties...
  3. ncbi Brentuximab vedotin (SGN-35) for relapsed CD30-positive lymphomas
    Anas Younes
    Department of Lymphoma and Myeloma, University of Texas M D Anderson Cancer Center, Houston, TX 77030, USA
    N Engl J Med 363:1812-21. 2010
    ....
  4. ncbi Enhancement of antitumor immunity by CTLA-4 blockade
    D R Leach
    Cancer Research Laboratory, University of California, Berkeley, CA 94720, USA
    Science 271:1734-6. 1996
    ..These results suggest that blockade of the inhibitory effects of CTLA-4 can allow for, and potentiate, effective immune responses against tumor cells...
  5. pmc Efficacy and safety of abatacept or infliximab vs placebo in ATTEST: a phase III, multi-centre, randomised, double-blind, placebo-controlled study in patients with rheumatoid arthritis and an inadequate response to methotrexate
    M Schiff
    Denver Arthritis Clinic, 200 Spruce Street 100, Denver, CO 80230, USA
    Ann Rheum Dis 67:1096-103. 2008
    ..The primary objective of this study was to evaluate the mean change from baseline in Disease Activity Score (based on erythrocyte sedimentation rates; DAS28 (ESR)) for the abatacept vs placebo groups at day 197...
  6. pmc Validation of the 28-joint Disease Activity Score (DAS28) and European League Against Rheumatism response criteria based on C-reactive protein against disease progression in patients with rheumatoid arthritis, and comparison with the DAS28 based on erythr
    G Wells
    Department of Epidemiology and Community Medicine, University of Ottawa, Canada
    Ann Rheum Dis 68:954-60. 2009
    ..To validate and compare the definition of the Disease Activity Score 28 based on C-reactive protein (DAS28 (CRP)) to the definition based on erythrocyte sedimentation rate (ESR)...
  7. pmc Clinical efficacy and safety of abatacept in methotrexate-naive patients with early rheumatoid arthritis and poor prognostic factors
    R Westhovens
    UZ Gasthuisberg, Department of Rheumatology, B 3000 Leuven, Belgium
    Ann Rheum Dis 68:1870-7. 2009
    ..To assess the efficacy and safety of abatacept in methotrexate-naive patients with early rheumatoid arthritis (RA) and poor prognostic factors...
  8. ncbi Brentuximab vedotin (SGN-35) in patients with relapsed or refractory systemic anaplastic large-cell lymphoma: results of a phase II study
    Barbara Pro
    Fox Chase Cancer Center, 333 Cottman Ave, Philadelphia, PA 19111 2497, USA
    J Clin Oncol 30:2190-6. 2012
    ..A phase II multicenter trial was conducted to evaluate the efficacy and safety of brentuximab vedotin in patients with relapsed or refractory systemic ALCL...
  9. ncbi Comparative effectiveness and safety of biological treatment options after tumour necrosis factor α inhibitor failure in rheumatoid arthritis: systematic review and indirect pairwise meta-analysis
    Monika Schoels
    2nd Department of Internal Medicine, Hietzing Hospital, Vienna, Austria
    Ann Rheum Dis 71:1303-8. 2012
    ..Optimal treatment for rheumatoid arthritis (RA) after inadequate response (IR) to tumour necrosis factor α inhibitors (TNFi) remains uncertain...
  10. ncbi Complexities of CD28/B7: CTLA-4 costimulatory pathways in autoimmunity and transplantation
    B Salomon
    The Committee on Immunology, Ben May Institute for Cancer Research and Department of Pathology, University of Chicago, Chicago, Illinois 60637, USA
    Annu Rev Immunol 19:225-52. 2001
    ..The implications of these complexities and the potential for use of these therapies in clinical immune intervention are discussed...
  11. pmc Results of a pivotal phase II study of brentuximab vedotin for patients with relapsed or refractory Hodgkin's lymphoma
    Anas Younes
    The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX 77030, USA
    J Clin Oncol 30:2183-9. 2012
    ..In phase I studies, brentuximab vedotin demonstrated significant activity with a favorable safety profile in patients with relapsed or refractory CD30-positive lymphomas...
  12. ncbi A phase III study of belatacept versus cyclosporine in kidney transplants from extended criteria donors (BENEFIT-EXT study)
    A Durrbach
    Bicetre Hospital, Kremlin Bicetre, IFRNT, Universite Paris Sud, France
    Am J Transplant 10:547-57. 2010
    ....
  13. ncbi BTLA is a lymphocyte inhibitory receptor with similarities to CTLA-4 and PD-1
    Norihiko Watanabe
    Department of Pathology and Immunology, Howard Hughes Medical Institute, Washington University School of Medicine, Box 8118, 660 South Euclid Avenue, St Louis, Missouri 63110, USA
    Nat Immunol 4:670-9. 2003
    ..B7x, a peripheral homolog of B7, is a ligand of BTLA. Thus, BTLA is a third inhibitory receptor on T lymphocytes with similarities to cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) and programmed death 1 (PD-1)...
  14. pmc Head-to-head comparison of subcutaneous abatacept versus adalimumab for rheumatoid arthritis: findings of a phase IIIb, multinational, prospective, randomized study
    Michael E Weinblatt
    Brigham and Women s Hospital, Boston, Massachusetts 02115, USA
    Arthritis Rheum 65:28-38. 2013
    ..Therefore, this study was undertaken as the first head-to-head comparison of subcutaneous (SC) abatacept and SC adalimumab, both administered along with background methotrexate (MTX), for the treatment of RA...
  15. pmc Long-term safety, efficacy and inhibition of radiographic progression with abatacept treatment in patients with rheumatoid arthritis and an inadequate response to methotrexate: 3-year results from the AIM trial
    Joel M Kremer
    Center for Rheumatology, Albany Medical College, 1367 Washington Ave, Albany, NY 12206, USA
    Ann Rheum Dis 70:1826-30. 2011
    ..To evaluate abatacept treatment over 3 years in patients with rheumatoid arthritis (RA) refractory to methotrexate (MTX)...
  16. pmc Subcutaneous abatacept versus intravenous abatacept: a phase IIIb noninferiority study in patients with an inadequate response to methotrexate
    M C Genovese
    Stanford University, Palo Alto, California 94304, USA
    Arthritis Rheum 63:2854-64. 2011
    ..To compare the efficacy and safety of subcutaneous (SC) and intravenous (IV) abatacept...
  17. ncbi Efficacy and safety of the selective co-stimulation modulator abatacept following 2 years of treatment in patients with rheumatoid arthritis and an inadequate response to anti-tumour necrosis factor therapy
    M C Genovese
    Stanford University, Division of Immunology and Rheumatology, 1000 Welch Road 203, Palo Alto, CA 94304, USA
    Ann Rheum Dis 67:547-54. 2008
    ..To evaluate the safety and efficacy of abatacept during 2 years of the ATTAIN (Abatacept Trial in Treatment of Anti-TNF INadequate responders) trial in patients with rheumatoid arthritis...
  18. pmc Immunologic self-tolerance maintained by CD25(+)CD4(+) regulatory T cells constitutively expressing cytotoxic T lymphocyte-associated antigen 4
    T Takahashi
    Department of Experimental Pathology, Institute for Frontier Medical Sciences, Kyoto University, Kyoto 606 8507, Japan
    J Exp Med 192:303-10. 2000
    ..This unique function of CTLA-4 could be exploited to potentiate T cell-mediated immunoregulation, and thereby to induce immunologic tolerance or to control autoimmunity...
  19. ncbi Phase I study of trastuzumab-DM1, an HER2 antibody-drug conjugate, given every 3 weeks to patients with HER2-positive metastatic breast cancer
    IAN E KROP
    Dana Farber Cancer Institute, 44 Binney Street, Boston, MA 02115, USA
    J Clin Oncol 28:2698-704. 2010
    ..This first-in-human study of T-DM1 evaluated safety, pharmacokinetics, and preliminary activity of T-DM1 in patients with advanced HER2-positive breast cancer...
  20. ncbi Rational development of LEA29Y (belatacept), a high-affinity variant of CTLA4-Ig with potent immunosuppressive properties
    Christian P Larsen
    Emory Transplant Center, Department of Surgery, School of Medicine, Emory University Atlanta, Georgia, USA
    Am J Transplant 5:443-53. 2005
    ..The use of immunoselective biologics may provide effective maintenance immunosuppression while avoiding the collateral toxicities associated with conventional immunsuppressants...
  21. ncbi Loss of CTLA-4 leads to massive lymphoproliferation and fatal multiorgan tissue destruction, revealing a critical negative regulatory role of CTLA-4
    E A Tivol
    Department of Pathology, Brigham and Women s Hospital, Boston, Massachusetts, USA
    Immunity 3:541-7. 1995
    ..In the absence of CTLA-4, peripheral T cells are activated, can spontaneously proliferate, and may mediate lethal tissue injury...
  22. pmc CTLA4-Ig and anti-CD40 ligand prevent renal allograft rejection in primates
    A D Kirk
    Division of Transplantation, University of Wisconsin Hospital, Madison, WI 53792, USA
    Proc Natl Acad Sci U S A 94:8789-94. 1997
    ....
  23. ncbi Antibody-drug conjugates designed to eradicate tumors with homogeneous and heterogeneous expression of the target antigen
    Yelena V Kovtun
    ImmunoGen, Inc, Cambridge, Massachusetts 02139, USA
    Cancer Res 66:3214-21. 2006
    ..Our data offer a rationale for developing optimally constructed antibody-drug conjugates for treating tumors that express the target antigen either in a homogeneous or heterogeneous manner...
  24. ncbi The efficacy and safety of abatacept in patients with non-life-threatening manifestations of systemic lupus erythematosus: results of a twelve-month, multicenter, exploratory, phase IIb, randomized, double-blind, placebo-controlled trial
    J T Merrill
    Oklahoma Medical Research Foundation, Oklahoma City, OK 73104, USA
    Arthritis Rheum 62:3077-87. 2010
    ..To evaluate abatacept therapy in patients with non-life-threatening systemic lupus erythematosus (SLE) and polyarthritis, discoid lesions, or pleuritis and/or pericarditis...
  25. pmc CTLA-4 is a second receptor for the B cell activation antigen B7
    P S Linsley
    Oncogen Division, Bristol Myers Squibb Pharmaceutical Research Institute, Seattle, Washington 98121
    J Exp Med 174:561-9. 1991
    ..Lymphocyte interactions involving the B7 counter-receptor are functionally important for alloantigen responses in vitro...
  26. ncbi Lymphoproliferative disorders with early lethality in mice deficient in Ctla-4
    P Waterhouse
    Department of Immunology, University of Toronto, Ontario, Canada
    Science 270:985-8. 1995
    ..Thus, CTLA-4 acts as a negative regulator of T cell activation and is vital for the control of lymphocyte homeostasis...
  27. ncbi Three-year outcomes from BENEFIT, a randomized, active-controlled, parallel-group study in adult kidney transplant recipients
    F Vincenti
    University of California, San Francisco, Kidney Transplant Service, San Francisco, CA, USA
    Am J Transplant 12:210-7. 2012
    ..Belatacept-treated patients maintained a high rate of patient and graft survival that was comparable to cyclosporine-treated patients, despite an early increased occurrence of acute rejection and PTLD...
  28. pmc The 6-month safety and efficacy of abatacept in patients with rheumatoid arthritis who underwent a washout after anti-tumour necrosis factor therapy or were directly switched to abatacept: the ARRIVE trial
    M Schiff
    University of Colorado, Greenwood Village, CO 80111, USA
    Ann Rheum Dis 68:1708-14. 2009
    ..To assess the safety, tolerability and efficacy of abatacept in patients with rheumatoid arthritis (RA) who had failed anti-tumour necrosis factor (TNF) therapy and were switched to abatacept directly or after completing washout...
  29. ncbi CD4+CD25high regulatory cells in human peripheral blood
    C Baecher-Allan
    Laboratory of Molecular Immunology, Center for Neurologic Diseases, Brigham and Women s Hospital, Boston, MA 02115
    J Immunol 167:1245-53. 2001
    ....
  30. ncbi Abatacept in the treatment of patients with psoriatic arthritis: results of a six-month, multicenter, randomized, double-blind, placebo-controlled, phase II trial
    Philip Mease
    University of Washington, Seattle, WA, USA
    Arthritis Rheum 63:939-48. 2011
    ..To assess the safety and efficacy of abatacept, a selective T cell costimulation modulator, in patients with psoriatic arthritis (PsA)...
  31. ncbi Tumor delivery and in vivo processing of disulfide-linked and thioether-linked antibody-maytansinoid conjugates
    Hans K Erickson
    ImmunoGen, Inc, Waltham, MA 02451, USA
    Bioconjug Chem 21:84-92. 2010
    ....
  32. ncbi In vitro and in vivo responses of advanced prostate tumors to PSMA ADC, an auristatin-conjugated antibody to prostate-specific membrane antigen
    Xinning Wang
    Department of Cancer Biology, Cleveland Clinic Foundation, Cleveland, Ohio, USA
    Mol Cancer Ther 10:1728-39. 2011
    ..This study defines determinants of antitumor activity of a novel ADC. The findings here support the clinical evaluation of this agent in advanced prostate cancer...
  33. pmc Therapeutic effect of cytotoxic T lymphocyte antigen 4/immunoglobulin on a murine model of primary biliary cirrhosis
    Amy Dhirapong
    Division of Rheumatology, Allergy, and Clinical Immunology, University of California at Davis, Davis, CA 95616, USA
    Hepatology 57:708-15. 2013
    ....
  34. ncbi CTLA-4 suppresses proximal TCR signaling in resting human CD4(+) T cells by inhibiting ZAP-70 Tyr(319) phosphorylation: a potential role for tyrosine phosphatases
    Christine Guntermann
    Laboratory of Lymphocyte Signaling and Development, Molecular Immunology Program, The Babraham Institute, Cambridge, United Kingdom
    J Immunol 168:4420-9. 2002
    ..Collectively, our findings suggest that CTLA-4 can act early during the immune response to regulate the threshold of T cell activation...
  35. ncbi Impact of drug conjugation on pharmacokinetics and tissue distribution of anti-STEAP1 antibody-drug conjugates in rats
    C Andrew Boswell
    Department of Pharmacokinetic and Pharmacodynamic Sciences, Genentech Research and Early Development, South San Francisco, California 94080, United States
    Bioconjug Chem 22:1994-2004. 2011
    ..Taken together, these results indicate that the degree of overall structural modification in anti-STEAP1-MMAE conjugates has a corresponding level of impact on both PK and tissue distribution...
  36. pmc Positive progress in immunoPET--not just a coincidence
    Katelyn E McCabe
    David Geffen School of Medicine at UCLA, Los Angeles, California, USA
    Cancer Biother Radiopharm 25:253-61. 2010
    ..Antibody-based PET probes constitute a valuable class of molecular imaging agents, and the progress made preclinically should expedite the transition of these targeted diagnostics to clinical applications...
  37. pmc Mode of action of abatacept in rheumatoid arthritis patients having failed tumour necrosis factor blockade: a histological, gene expression and dynamic magnetic resonance imaging pilot study
    M H Buch
    Academic Unit of Musculoskeletal Disease, University of Leeds, Leeds, UK
    Ann Rheum Dis 68:1220-7. 2009
    ..The aim of this study was to determine the synovial effect of abatacept in patients with RA and an inadequate response to tumour necrosis factor alpha (TNFalpha) blocking therapy...
  38. pmc Evaluation of abatacept administered subcutaneously in adults with active rheumatoid arthritis: impact of withdrawal and reintroduction on immunogenicity, efficacy and safety (phase Iiib ALLOW study)
    Jeffrey Kaine
    Sarasota Arthritis Research Center, 1945 Versailles Street 101, Sarasota, FL 34239, USA
    Ann Rheum Dis 71:38-44. 2012
    ..To assess the effect of a temporary interruption in subcutaneous (SC) abatacept on immunogenicity, safety and efficacy in patients with active rheumatoid arthritis despite methotrexate in a phase III trial...
  39. ncbi Crystal structure of the B7-1/CTLA-4 complex that inhibits human immune responses
    C C Stamper
    Departments of Biological Chemistry and Musculoskeletal Sciences, Wyeth Research, 87 Cambridge Park Drive, Cambridge, Massachusetts 02140, USA
    Nature 410:608-11. 2001
    ..This zipper-like oligomerization provides the structural basis for forming unusually stable signalling complexes at the T-cell surface, underscoring the importance of potent inhibitory signalling in human immune responses...
  40. ncbi Targeted drug delivery using immunoconjugates: principles and applications
    Maria Valentina Pasquetto
    Department of Experimental Medicine, Section of General Pathology, University of Pavia, Via Ferrata, Italy
    J Immunother 34:611-28. 2011
    Antibody-drug conjugates (also known as "immunoconjugates") have only recently entered the arsenal of anticancer drugs, but the number of undergoing clinical trials including them is ever increasing and most therapeutic antibodies are now ..
  41. ncbi Immunoconjugates against solid tumors: mind the gap
    A D Ricart
    BioTherapeutics Research and Development, La Jolla Laboratories, Pfizer, San Diego, California, USA
    Clin Pharmacol Ther 89:513-23. 2011
    ..Promising immunoconjugates are in development: immunoconjugates targeting the prostate-specific membrane antigen, trastuzumab-DM1, ..
  42. ncbi B7/CD28 costimulation is essential for the homeostasis of the CD4+CD25+ immunoregulatory T cells that control autoimmune diabetes
    B Salomon
    Committee on Immunology, Ben May Institute for Cancer Research and Department of Pathology, University of Chicago, Illinois 60637, USA
    Immunity 12:431-40. 2000
    ..The results suggest that the CD28/ B7 costimulatory pathway is essential for the development and homeostasis of regulatory T cells that control spontaneous autoimmune diseases...
  43. ncbi Sustained disease remission and inhibition of radiographic progression in methotrexate-naive patients with rheumatoid arthritis and poor prognostic factors treated with abatacept: 2-year outcomes
    J Bathon
    College of Physician and Surgeons, Columbia University, 630 West 168th Street, P and S 10 445, New York, NY 10023, USA
    Ann Rheum Dis 70:1949-56. 2011
    ..To assess the efficacy and safety of abatacept plus methotrexate versus methotrexate alone in early erosive rheumatoid arthritis (RA)...
  44. ncbi Cutting edge: reversal of murine lupus nephritis with CTLA4Ig and cyclophosphamide
    D I Daikh
    Department of Medicine, Department of Veterans Affairs Medical Center and the University of California, San Francisco, CA 94121, USA
    J Immunol 166:2913-6. 2001
    ..This striking reversal of proteinuria is unprecedented in animal models of SLE...
  45. pmc High CD21 expression inhibits internalization of anti-CD19 antibodies and cytotoxicity of an anti-CD19-drug conjugate
    Gladys S Ingle
    Department of Molecular Biology, Genentech, Inc, South San Francisco, CA 94080, USA
    Br J Haematol 140:46-58. 2008
    ..This may have possible clinical implications, as anti-CD21 immunohistochemistry revealed only approximately 30% of 54 diffuse large B-cell lymphoma patients lack CD21 expression...
  46. ncbi Porcine CTLA4-Ig prolong islet xenografts in rats by downregulating the direct pathway of T-cell activation
    Chao Zhai
    Department of Hepatobiliary Surgery, First Affiliated Hospital, Medical College, Xi an Jiaotong University, Xi an, China
    Xenotransplantation 18:40-5. 2011
    ..Porcine pancreatic islets fused with pCTLA4-Ig were transplanted into diabetic rats. Xenografts survival was observed, and the underlying immunological rejection mechanisms were investigated...
  47. ncbi Pharmacokinetic considerations for antibody drug conjugates
    Kedan Lin
    Genentech Research and Early Development, South San Francisco, California 94080, USA
    Pharm Res 29:2354-66. 2012
    ..The disposition of ADCs and the utility of PKPD modeling are discussed in the context of providing guidance to assist in the successful development of these complex molecules...
  48. ncbi Epratuzumab-SN-38: a new antibody-drug conjugate for the therapy of hematologic malignancies
    Robert M Sharkey
    Garden State Cancer Center, 300 American Road, Morris Plains, New Jersey 07950, USA
    Mol Cancer Ther 11:224-34. 2012
    ..Thus, Emab-SN-38 is active in lymphoma and leukemia at doses well below toxic levels and therefore represents a new promising agent with therapeutic potential alone or combined with anti-CD20 antibody therapy...
  49. ncbi Trastuzumab-DM1 (T-DM1) retains all the mechanisms of action of trastuzumab and efficiently inhibits growth of lapatinib insensitive breast cancer
    Teemu T Junttila
    Research Oncology, Genentech, Inc, 1 DNA Way, Mailstop 72, South San Francisco, CA 94080, USA
    Breast Cancer Res Treat 128:347-56. 2011
    ..Here we report that T-DM1 retains the mechanisms of action of unconjugated trastuzumab and is active against lapatinib resistant cell lines and tumors...
  50. ncbi Sequential use of biologic therapy in rheumatoid arthritis
    Maya H Buch
    Leeds Institute of Molecular Medicine, University of Leeds, Leeds Teaching Hospitals Trust, UK
    Curr Opin Rheumatol 22:321-9. 2010
    ..This review will address the evidence to date on use of successive targeted agents...
  51. ncbi Association of the T-cell regulatory gene CTLA4 with susceptibility to autoimmune disease
    Hironori Ueda
    Juvenile Diabetes Research Foundation Wellcome Trust Diabetes and Inflammation Laboratory, Cambridge Institute for Medical Research, University of Cambridge, Wellcome Trust MRC Building, Cambridge, CB2 2XY, UK
    Nature 423:506-11. 2003
    ..Genetic mapping of variants conferring a small disease risk can identify pathways in complex disorders, as exemplified by our discovery of inherited, quantitative alterations of CTLA4 contributing to autoimmune tissue destruction...
  52. ncbi Combination immunotherapy of primary prostate cancer in a transgenic mouse model using CTLA-4 blockade
    A A Hurwitz
    Cancer Research Laboratory, University of California, Berkeley 94720, USA
    Cancer Res 60:2444-8. 2000
    ..These findings demonstrate that this combinatorial treatment can elicit a potent antiprostate response and suggest potential of this approach for treatment of prostate cancer...
  53. ncbi CTLA-4 can function as a negative regulator of T cell activation
    T L Walunas
    University of Chicago, Illinois 60637
    Immunity 1:405-13. 1994
    ..Together, these results suggest that the MAb may obstruct the interaction of CTLA-4 with its natural ligand and block a negative signal, or directly signal T cells to down-regulate immune function...
  54. ncbi The next generation of antibody-drug conjugates comes of age
    Alain Beck
    Department of Physico Chemistry, Centre d Immunologie Pierre Fabre CIPF, St Julien en Genevois 74164, France
    Discov Med 10:329-39. 2010
    ..Several examples of ADCs are presented with emphasis on three major molecules currently in late clinical development as well as next generation thio-mAbs conjugates with improved therapeutic index...
  55. ncbi Control of peripheral T-cell tolerance and autoimmunity via the CTLA-4 and PD-1 pathways
    Brian T Fife
    Department of Medicine, UCSF Diabetes Center, University of California, San Francisco, CA 94113, USA
    Immunol Rev 224:166-82. 2008
    ....
  56. pmc Human cd25(+)cd4(+) t regulatory cells suppress naive and memory T cell proliferation and can be expanded in vitro without loss of function
    M K Levings
    San Raffaele Telethon Institute for Gene Therapy (HSR-TIGET, Via Olgettina 58, Milan, Italy 20132
    J Exp Med 193:1295-302. 2001
    ....
  57. pmc Costimulation blockade inhibits allergic sensitization but does not affect established allergy in a murine model of grass pollen allergy
    Birgit Linhart
    Christian Doppler Laboratory for Allergy Research, Division of Immunopathology, Department of Pathophysiology, Center of Physiology and Pathophysiology, Medical University of Vienna, Waehringer Guertel 18 20, A 1090 Vienna, Austria
    J Immunol 178:3924-31. 2007
    ..Our results indicate that T cell suppression alone without active immune regulation or a shifting of the Th2/Th1 balance is not sufficient for the treatment of established IgE responses in an allergy...
  58. ncbi Cutting edge: Regulatory T cells from lung cancer patients directly inhibit autologous T cell proliferation
    Edward Y Woo
    Department of Surgery, University of Pennsylvania Medical Center, Philadelphia, PA 19104, USA
    J Immunol 168:4272-6. 2002
    ..Together these results suggest that the CD4(+)CD25(+) T cells found in lung tumors selectively inhibit the host immune response and therefore could contribute to the progression of lung cancer...
  59. ncbi Lymphoproliferation in CTLA-4-deficient mice is mediated by costimulation-dependent activation of CD4+ T cells
    C A Chambers
    Howard Hughes Medical Institute, Department of Molecular and Cellular Biology, University of California, Berkeley 94720, USA
    Immunity 7:885-95. 1997
    ..These results demonstrate that CD4+ T cells initiate the phenotype in the CTLA-4(-/-) mice. Further, these results suggest that the role of CTLA-4 in peripheral CD4+ versus CD8+ T cell homeostasis is distinct...
  60. ncbi Antibody-drug conjugates: linking cytotoxic payloads to monoclonal antibodies
    Laurent Ducry
    Lonza Ltd, CH 3930 Visp, Switzerland
    Bioconjug Chem 21:5-13. 2010
    ..Recent advances have resulted in linkers having increased stability in the bloodstream while allowing efficient payload release within the tumor cell...
  61. pmc A novel clinically relevant strategy to abrogate autoimmunity and regulate alloimmunity in NOD mice
    Andrea Vergani
    Transplantation Research Center, Children s Hospital and Brigham and Women s Hospital, Harvard Medical School, Boston, Massachusetts, USA
    Diabetes 59:2253-64. 2010
    ....
  62. ncbi The role of the CD28 receptor during T cell responses to antigen
    P S Linsley
    Department of Cellular Immunology, Bristol Myers Squibb Pharmaceutical Research Institute, Seattle, Washington 98121
    Annu Rev Immunol 11:191-212. 1993
    ..The CD28 costimulatory receptor represents a novel target for immunosuppressive drugs...
  63. ncbi Effects of drug loading on the antitumor activity of a monoclonal antibody drug conjugate
    Kevin J Hamblett
    Seattle Genetics, Inc, Bothell, Washington 98021, USA
    Clin Cancer Res 10:7063-70. 2004
    ..To determine the effect of drug loading on antibody-drug conjugate therapeutic potential, we assessed cAC10 antibody-drug conjugates containing different drug-mAb ratios in vitro and in vivo...
  64. ncbi Tyrosine phosphorylation controls internalization of CTLA-4 by regulating its interaction with clathrin-associated adaptor complex AP-2
    T Shiratori
    Division of Molecular Genetics, Center for Biomedical Science, Chiba University School of Medicine, Chuo Ku, Japan
    Immunity 6:583-9. 1997
    ..Our results suggest that the phosphorylation state of a single tyrosine residue determines whether CTLA-4 delivers a negative signal or is internalized...
  65. pmc The effect of costimulatory and interleukin 2 receptor blockade on regulatory T cells in renal transplantation
    J A Bluestone
    Diabetes Center, Department of Medicine, University of California San Francisco, CA, USA
    Am J Transplant 8:2086-96. 2008
    ....
  66. pmc Risk of serious infections during rituximab, abatacept and anakinra treatments for rheumatoid arthritis: meta-analyses of randomised placebo-controlled trials
    C Salliot
    Rene Descartes University, Medicine Faculty, AP HP, Cochin Hospital, Rheumatology B Department, Paris, France
    Ann Rheum Dis 68:25-32. 2009
    ..Recently, new biological agents have become available. Their safety is an important issue...
  67. ncbi Safety and efficacy of the selective costimulation modulator abatacept in patients with rheumatoid arthritis receiving background methotrexate: a 5-year extended phase IIB study
    Rene Westhovens
    Department of Rheumatology, KU Leuven, Herestraat 49, B 3000 Leuven, Belgium
    J Rheumatol 36:736-42. 2009
    ..To evaluate the safety and efficacy of abatacept plus methotrexate (MTX) over 5 years in patients with rheumatoid arthritis...
  68. pmc 89Zr-DFO-J591 for immunoPET of prostate-specific membrane antigen expression in vivo
    Jason P Holland
    Radiochemistry Service, Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, New York 10065, USA
    J Nucl Med 51:1293-300. 2010
    ....
  69. ncbi CTLA-4 regulates induction of anergy in vivo
    R J Greenwald
    Immunology Research Division, Department of Pathology, Brigham and Women s Hospital, Harvard Medical School, Boston, MA, 02115, USA
    Immunity 14:145-55. 2001
    ..Thus, CTLA-4 has an essential role in determining the outcome of T cell encounter with a tolerogenic stimulus...
  70. ncbi Control of memory CD4 T cell recall by the CD28/B7 costimulatory pathway
    Modesta P Ndejembi
    Division of Transplantation, University of Maryland School of Medicine, 685 West Baltimore Street, Baltimore, MD 21201, USA
    J Immunol 177:7698-706. 2006
    ....
  71. pmc Unique chemotactic response profile and specific expression of chemokine receptors CCR4 and CCR8 by CD4(+)CD25(+) regulatory T cells
    A Iellem
    Roche Milano Ricerche, Milano I-20132, Italy
    J Exp Med 194:847-53. 2001
    ..Overall, these results suggest that CCR4 and/or CCR8 may guide Treg cells to sites of antigen presentation in secondary lymphoid tissues and inflamed areas to attenuate T cell activation...
  72. ncbi Abatacept binds to the Fc receptor CD64 but does not mediate complement-dependent cytotoxicity or antibody-dependent cellular cytotoxicity
    Patricia M Davis
    Discovery Biology, Bristol Myers Squibb Pharmaceutical Research Institute, Princeton, NJ 08543, USA
    J Rheumatol 34:2204-10. 2007
    ..To assess the ability of abatacept to mediate complement-dependent cytotoxicity (CDC) or antibody-dependent cellular cytotoxicity (ADCC) of antigen-presenting cells, and to characterize the binding of abatacept to the 3 Fc receptor classes...
  73. ncbi Ligation of B7-1/B7-2 by human CD4+ T cells triggers indoleamine 2,3-dioxygenase activity in dendritic cells
    David H Munn
    Institute of Molecular Medicine and Genetics and Departments of Pediatrics, Medical College of Georgia, Augusta, GA 30912, USA
    J Immunol 172:4100-10. 2004
    ..We hypothesize that IDO activation via engagement of B7-1/B7-2 molecules on DCs, specifically, engagement by CTLA4 expressed on regulatory CD4(+) T cells, may function as a physiologic regulator of T cell responses in vivo...
  74. ncbi Improving the efficacy of antibody-based cancer therapies
    P Carter
    Immunex, Seattle, Washington 98101, USA
    Nat Rev Cancer 1:118-29. 2001
    ..Although antibodies have yet to achieve the ultimate goal of curing cancer, many innovative approaches stand poised to improve the efficacy of antibody-based therapies...
  75. ncbi Targeting of antigens to activated dendritic cells in vivo cures metastatic melanoma in mice
    Karsten Mahnke
    Department of Dermatology, University of Heidelberg, Heidelberg, Germany
    Cancer Res 65:7007-12. 2005
    ..Thus, these data show that targeting of dendritic cells in situ by the means of antibody-antigen conjugates may be a novel way to induce long-lasting antitumor immunity...
  76. ncbi cAC10-vcMMAE, an anti-CD30-monomethyl auristatin E conjugate with potent and selective antitumor activity
    Joseph A Francisco
    Seattle Genetics, Bothell, WA 98021, USA
    Blood 102:1458-65. 2003
    ..Mice treated at 30 mg/kg cAC10-vcMMAE showed no signs of toxicity. These data indicate that cAC10-vcMMAE may be a highly effective and selective therapy for the treatment of CD30+ neoplasias...
  77. ncbi A phase III study of belatacept-based immunosuppression regimens versus cyclosporine in renal transplant recipients (BENEFIT study)
    F Vincenti
    Kidney Transplant Service, University of California San Francisco, San Francisco, CA, USA
    Am J Transplant 10:535-46. 2010
    ..Belatacept was associated with superior renal function and similar patient/graft survival versus cyclosporine at 1 year posttransplant, despite a higher rate of early acute rejection...
  78. ncbi Interaction of CTLA-4 with the clathrin-associated protein AP50 results in ligand-independent endocytosis that limits cell surface expression
    E Chuang
    Gwen Knapp Center for Lupus and Immunology Research, Department of Molecular Genetics and Cell Biology, The University of Chicago, IL 60637, USA
    J Immunol 159:144-51. 1997
    ..Together these data suggest that the interaction of CTLA-4 with AP50 plays an important role in regulating the cell surface expression of CTLA-4...
  79. ncbi CTLA-4: a key regulatory point in the control of autoimmune disease
    Kenneth J Scalapino
    Department of Medicine, Division of Rheumatology, University of California, San Francisco, San Francisco, CA 94121, USA
    Immunol Rev 223:143-55. 2008
    ..Elucidating the role of CTLA-4 in immune tolerance has also led to a number of therapeutic applications, particularly in the treatment of malignancy and autoimmune disease...
  80. ncbi CTLA-4-Ig therapy diminishes the frequency but enhances the function of Treg cells in patients with rheumatoid arthritis
    Crisol Alvarez-Quiroga
    Department of Immunology, Facultad de Medicina, UASLP, Ave V Carranza 2405, 78210, San Luis Potosi, SLP, Mexico
    J Clin Immunol 31:588-95. 2011
    ..In contrast, the regulatory function of CD4+CD25+ lymphocytes was significantly enhanced after the administration of Abatacept. Our data suggest that CTLA-4-Ig exerts a complex and interesting effect on Treg cells in patients with RA...
  81. pmc Interaction of CTLA-4 with AP50, a clathrin-coated pit adaptor protein
    Y Zhang
    Department of Molecular and Cellular Biology and Cancer Research Laboratory, University of California, Berkeley, CA 94720, USA
    Proc Natl Acad Sci U S A 94:9273-8. 1997
    ..These results suggest that AP50 and the coated pit adaptor complex AP2 may play an important role in regulating the intracellular trafficking and function of CTLA-4...
  82. ncbi In vivo drug-linker stability of an anti-CD30 dipeptide-linked auristatin immunoconjugate
    Russell J Sanderson
    Seattle Genetics Inc, 21813 30th Drive Southeast, Bothell, WA 98021, USA
    Clin Cancer Res 11:843-52. 2005
    ..These data represent the longest reported drug-linker half-life to date and provide the basis for the pronounced specificity and antitumor activity of cAC10-valine-citrulline-MMAE...
  83. ncbi Anti-CD22-MCC-DM1: an antibody-drug conjugate with a stable linker for the treatment of non-Hodgkin's lymphoma
    A G Polson
    Research and Early Development, Genentech, South San Francisco, CA 94080, USA
    Leukemia 24:1566-73. 2010
    ..These results suggest that anti-CD22-MCC-DM1 has an efficacy, safety and pharmacodynamic profile that support its use as a treatment for NHL...
  84. ncbi Belatacept: a new biologic and its role in kidney transplantation
    Victoria C H Su
    Toronto Western Hospital, University Health Network, Toronto, Ontario, Canada
    Ann Pharmacother 46:57-67. 2012
    ..To review the pharmacology, efficacy, safety, and role of belatacept in maintenance immunosuppression in adult kidney transplant recipients (KTR)...
  85. pmc Five-year safety and efficacy of belatacept in renal transplantation
    Flavio Vincenti
    Division of Nephrology, University of California, San Francisco, 505 Parnassus Avenue, Moffitt 884, San Francisco, CA 94143 0780, USA
    J Am Soc Nephrol 21:1587-96. 2010
    ..In conclusion, this study demonstrated high patient persistence with intravenous belatacept, stable renal function, predictable pharmacokinetics, and good safety with belatacept over 5 years...
  86. ncbi Combined gene therapy with adenovirus vectors containing CTLA4Ig and CD40Ig prolongs survival of composite tissue allografts in rat model
    Kohei Kanaya
    Division of Molecular Immunology, Institute for Genetic Medicine, Hokkaido University, Sapporo, Japan
    Transplantation 75:275-81. 2003
    ..Therefore, we examined the effect of adenovirus-mediated gene transfer of CTLA4Ig or CD40Ig gene or both in composite tissue allotransplantation...
  87. ncbi Contribution of linker stability to the activities of anticancer immunoconjugates
    Stephen C Alley
    Seattle Genetics, Inc, 21823 30th Drive SE, Bothell, WA 98021, USA
    Bioconjug Chem 19:759-65. 2008
    ..In summary, the data indicate that new linkers can be obtained with improved in vivo stability by replacing the maleimide with an acetamide, but the resulting ADCs had similar tolerability and activity profiles...
  88. pmc Imaging DNA damage in vivo using gammaH2AX-targeted immunoconjugates
    Bart Cornelissen
    CR UK MRC Gray Institute for Radiation Oncology and Biology, University of Oxford, Oxford, United Kingdom
    Cancer Res 71:4539-49. 2011
    ..Toward this end, we have developed fluorophore- and radioisotope-labeled immunoconjugates to target a DDR signaling protein, phosphorylated histone H2A variant H2AX (γH2AX), which forms foci at ..
  89. ncbi Prolonged allograft survival but no tolerance induction by modulating CD28 antibody JJ319 after high-responder rat heart transplantation
    T J Dengler
    Department of Cardiology, Medical University Hospital, University of Heidelberg, Germany
    Transplantation 67:392-8. 1999
    ..Because this approach also inhibits a potentially tolerizing signal through CTLA-4, selective blockade of CD28 ligation might induce more profound immunosuppression and transplant tolerance...
  90. pmc ACR70-disease activity score remission achievement from switches between all the available biological agents in rheumatoid arthritis: a systematic review of the literature
    Stefano Alivernini
    Division of Rheumatology, School of Medicine, Catholic University of the Sacred Heart, Largo F Vito 1, 00168 Rome, Italy
    Arthritis Res Ther 11:R163. 2009
    ....
  91. pmc CTLA4-Ig interacts with cultured synovial macrophages from rheumatoid arthritis patients and downregulates cytokine production
    Maurizio Cutolo
    Research Laboratories and Academic Unit of Clinical Rheumatology, Department of Internal Medicine, University of Genova, Viale Benedetto XV, 16132 Genova, Italy
    Arthritis Res Ther 11:R176. 2009
    ..In addition, the anti-inflammatory effects of CTLA4-Ig on co-cultures of RA SM and M with activated T cells were tested...
  92. pmc Combination of the anti-CD30-auristatin-E antibody-drug conjugate (SGN-35) with chemotherapy improves antitumour activity in Hodgkin lymphoma
    Ezogelin Oflazoglu
    Department of Preclinical Therapeutics, Seattle Genetics Inc, Bothell, WA 98021, USA
    Br J Haematol 142:69-73. 2008
    ..Improved efficacy was also observed in high tumour burden models, indicating that combining ADCs with chemotherapeutic agents may be advantageous for the treatment of patients with relapsed or refractory HL...
  93. ncbi Combined coinhibitory and costimulatory modulation with anti-BTLA and CTLA4Ig facilitates tolerance in murine islet allografts
    W Truong
    The Surgical Medical Research Institute, Department of Surgery, Faculty of Medicine, The University of Alberta, Edmonton, Alberta, Canada
    Am J Transplant 7:2663-74. 2007
    ..We conclude that targeting the BTLA pathway in conjunction with CTLA4Ig costimulatory blockade may be a useful strategy for promoting immunological tolerance in murine islet allografts...
  94. ncbi Star-shaped immunoglobulin-containing HPMA-based conjugates with doxorubicin for cancer therapy
    Tomas Etrych
    Institute of Macromolecular Chemistry, Academy of Sciences of the Czech Republic, Prague 6, Czech Republic
    J Control Release 122:31-8. 2007
    ..The star-shaped conjugates containing immunoglobulin showed a significantly higher antitumor activity in vivo than immunoglobulin-free non-targeted polymer conjugates when tested in mice bearing EL4 T-cell lymphoma...
  95. ncbi Abatacept in subjects who switch from intravenous to subcutaneous therapy: results from the phase IIIb ATTUNE study
    Edward Clark Keystone
    Rheumatology Department, Mount Sinai Hospital, Toronto, Canada
    Ann Rheum Dis 71:857-61. 2012
    ..To assess safety, immunogenicity and efficacy in rheumatoid arthritis (RA) patients switched from long-term intravenous to subcutaneous (SC) abatacept...
  96. ncbi Achieving permanent survival of islet xenografts by independent manipulation of direct and indirect T-cell responses
    Vincenzo Mirenda
    Department of Immunology, Division of Medicine, Imperial College London, UK
    Diabetes 54:1048-55. 2005
    ..These results suggest that a similar approach could have clinical utility in porcine islet xenotransplantation...
  97. pmc Near-infrared theranostic photoimmunotherapy (PIT): repeated exposure of light enhances the effect of immunoconjugate
    Makoto Mitsunaga
    Molecular Imaging Program, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892 1088, USA
    Bioconjug Chem 23:604-9. 2012
    ..Therapeutic effects were monitored using IR700 fluorescent signal. PIT is a promising highly selective and clinically feasible theranostic method for treatment of mAb-binding tumors with minimal off-target effects...
  98. ncbi Long-term safety and efficacy of abatacept in children with juvenile idiopathic arthritis
    Nicolino Ruperto
    Istituto di Ricovero e Cura a Carattere Scientifico G Gaslini, Genoa, Italy
    Arthritis Rheum 62:1792-802. 2010
    ..Here, we report results from the long-term extension (LTE) phase of that study...
  99. ncbi Engineered antibody-drug conjugates with defined sites and stoichiometries of drug attachment
    Charlotte F McDonagh
    Seattle Genetics, Inc 21823 30th Drive SE, Bothell, WA 98021, USA
    Protein Eng Des Sel 19:299-307. 2006
    ..Our strategy for generating antibody-drug conjugates with defined sites and stoichiometries of drug loading is potentially broadly applicable to other antibodies as it involves engineering of constant domains...
  100. ncbi Abatacept improves health-related quality of life, pain, sleep quality, and daily participation in subjects with juvenile idiopathic arthritis
    Nicolino Ruperto
    Universita di Genova, Genoa, Italy
    Arthritis Care Res (Hoboken) 62:1542-51. 2010
    ..To assess health-related quality of life (HRQOL) in abatacept-treated children/adolescents with juvenile idiopathic arthritis (JIA)...
  101. ncbi Photosensitizer-antibody conjugates for detection and therapy of cancer
    G A M S van Dongen
    Department of Otolaryngology Head and Neck Surgery, VU University Medical Center, De Boelelaan 1117, P O Box 7057, 1007 MB Amsterdam, The Netherlands
    Adv Drug Deliv Rev 56:31-52. 2004
    ..Results obtained thus far with PIT in in vitro and in vivo model systems are discussed. Despite the encouraging progress made, showing the high selectivity of photoimmunoconjugates, PIT still awaits initial clinical evaluation...

Research Grants62

  1. Impact of genetic variation on response to GO therapy in COG-AML clinical trials
    ROLAND BRUNO WALTER; Fiscal Year: 2013
    ..However, our findings may extend to second-generation immunoconjugates targeting CD33 as well...
  2. TWO COMPARTMENT MODELS TO IMPROVE BRAIN TUMOR THERAPY
    Edward A Neuwelt; Fiscal Year: 2012
    ..treatment approaches and neurotoxicity in brain tumor models, the effect of immunotherapy, drug- and radio-immunoconjugates, and combination therapies will be assessed in a new rat intracerebral model of CNS lymphoma (CNSL) and in ..
  3. AML Stem Cell Heterogeneity: Implications for Gemtuzumab Ozogomicin-based Therapy
    Roland Walter; Fiscal Year: 2009
    ..Research will also be performed to find out which patients benefit most from these therapies and to see how these drug combinations precisely work together with GO to kill leukemia cells. ..
  4. Targeted Lipopolyplexes for Oligonucleotide Delivery to AML
    Robert J Lee; Fiscal Year: 2012
    ..be achieved through targeted delivery of GTI-2040 using multifunctional nanovehicles consisting of immunoconjugates of lipopolyplexes (ILPs)...
  5. Development of Novel Immunoconjugates for Application in Cancer Therapeutics
    DOUGLAS DEAN YOUNG; Fiscal Year: 2010
    ..Most notably, the generation of well-defined immunoconjugates (antibodies linked to a variety of chemical entities) can alter the paradigm of cancer treatment, affording ..
  6. Probing Tumor Microenvironment Using Nanotechnology
    Rakesh K Jain; Fiscal Year: 2012
    ..They will develop novel nanocrystal (quantum dot) constructs, biosensors, and immunoconjugates which are not only essential for all three projects in this BRP but also provide a new direction in ..
  7. M.D. Anderson Gynecologic SPORE for Uterine Cancers
    KAREN HSIEH LU; Fiscal Year: 2013
    ..Four Cores will support these projects. Core A (Administrative Core), Core B (Pathology Core), Core C Biomarkers Core, and Core D (Biostatistics and Bioinformatics Core). ..
  8. Modular immunoconjugates
    VAUGHN VASIL SMIDER; Fiscal Year: 2010
    ..This "lego" block assembly process will allow a vast array of combinatorial protein theranostic modules to be created and evaluated against a myriad of diseases. ..
  9. NOVEL APPROACHES TO RADIO-IMMUNOCONJUGATE DOSIMETRY
    Lee Chin; Fiscal Year: 1991
    ..The dosimetric tools developed here will be appropriate for later application to clinical radio-immunotherapy...
  10. New Strategies for Photoimmunodetection/therapy
    MARK DAVID SAVELLANO; Fiscal Year: 2010
    ..In Aim 1, novel fluorochrome-photosensitizer immunoconjugates (FPICs) will be developed that should enable concomitant PID and PIT...
  11. New management of vocal scar with antibody/ICG guided laser
    Zhi Wang; Fiscal Year: 2013
    ..We expect this new treatment, if successful in this study, will provide a promising management for this problem, and it would be safe and convenient as an office-based procedure. ..
  12. Immunotherapy for Pulmonary Anthrax
    KEITH WYCOFF; Fiscal Year: 2003
    ..We will combine our experience in producing functional antibodies and immunoconjugates in transgenic plants with the Anthrax Toxin Receptor (ATR), and with high-affinity antibodies against the ..
  13. ENZYME IMMUNOAUGMENTATION OF HODGKIN'S DISEASE
    Michael Samoszuk; Fiscal Year: 1993
    ....
  14. MAb-based targeted chemotherapy of lung cancer
    Serengulam Govindan; Fiscal Year: 2009
    ..The ultimate goal of the proposed project is to develop a safer and more efficacious targeted chemotherapy of non-small cell lung cancer using a tumor-selective monoclonal antibody and the highly potent form of the cancer drug, CPT-11. ..
  15. Radioactive Nanoparticle Immunoconjugates for the Treatment of Solid Tumors
    Gregory Adams; Fiscal Year: 2009
    ..We hypothesize that this limitation could be overcome by increasing the specific activity of the immunoconjugates through the use of radioactive nanoparticles...
  16. NOVEL IMMUNOCONJUGATE APPROACHES
    Carl Wilhelm Vogel; Fiscal Year: 1990
    ..The new solid-phase methods will allow the synthesis of immunoconjugates containing the two reactants at a predetermined ratio (usually 1:1) with the least possible inactivation of ..
  17. Evaluation of novel cytotoxic compounds for immunoconjugates
    STANLEY BELL; Fiscal Year: 2007
    ..approach, which is particularly suited for anticancer therapy, involves Antibody-Drug Conjugates (ADCs), or immunoconjugates, and has experienced limited success in the past two decades...
  18. Modulation of B-cell tolerance by coreceptor molecules
    ROBERT RICKERT; Fiscal Year: 2005
    ..A similar approach will be used to form immunoconjugates of the Sm ribonucleoprotein and C3d to create a model of systemic lupus erythematosus (SLE)...
  19. ISOLATION AND CHARACTERIZATION OF PEYER'S PATCH M CELLS
    Jacques Pappo; Fiscal Year: 1993
    ..Monoclonal antibody-ricin A chain immunoconjugates will be used to immunotarget M cells in vivo...
  20. X-Ray Guided Drug Delivery Systems
    Dennis Hallahan; Fiscal Year: 2004
    ..The limitation of other forms of site-specific drug delivery (immunoconjugates and gene therapy) includes specificity for particular tumors, nonspecific delivery to other organs (eg...
  21. PEPTIDE DEGRADATION IN POLYMER MATRICES
    Elizabeth Topp; Fiscal Year: 2001
    Peptide and polypeptide drugs such as interferons, immunoconjugates, tissue plasminogen activator, human growth hormone and erythropoeitin, made available by the biotechnological revolution, are now entering the marketplace and presenting ..
  22. NOVEL RADIOIMMUNOTHERAPY FOR LYMPHOMA
    James Butrynski; Fiscal Year: 2001
    ..abstract_text> ..
  23. RADIOIMMUNOTHERAPY STRATEGIES IN NONHODGKINS LYMPHOMAS
    MELISSA CORCORAN; Fiscal Year: 1999
    ....
  24. Tumor Neovasculature Vector Targeting
    Albert Deisseroth; Fiscal Year: 2003
    ..Because the protocol should be applicable to a broad range of human solid tumors, a favorable outcome for the melanoma trial could lead to a new treatment not only for melanoma but also for other types of cancer. ..
  25. ELECTRON DOSIMETRY IN RADIOIMMUNOTHERAPY
    Cheuk Kwok; Fiscal Year: 1991
    Radiolabeled immunoconjugates against tumor-associated antigens have shown promise as both diagnostic and therapeutic agents in-vitro, in human tumor implants in animals, and in selected groups of cancer patients with metastatic lesions...
  26. GLYCOCONJUGATES IN PANCREATIC CANCER
    Young Kim; Fiscal Year: 2002
    ..Studies on the immunology of mucins will focus on: 1) increasing the effectiveness of Nd2 immunoconjugates; 2) producing new antisera against MUC3 mucin and quantitating circulating levels of MUC3 to determine if ..
  27. PEPTIDE DEGRADATION IN POLYMER MATRICES
    Elizabeth Topp; Fiscal Year: 2003
    Peptide and polypeptide drugs such as interferons, immunoconjugates, tissue plasminogen activator, human growth hormone and erythropoeitin, made available by the biotechnological revolution, are now entering the marketplace and presenting ..
  28. Potent Monoclonal Antibody Drug Conjugates
    Peter Senter; Fiscal Year: 2001
    ..This would constitute a major advancement in the clinical treatment of cancer. ..
  29. TARGETED IMMUNOTHERAPY FOR TUMOR EXPRESSING GRP RECEPTOR
    Tibor Keler; Fiscal Year: 2000
    ..Development of such therapeutics are greatly needed for SCCL for which currently available treatments provide only short-term remissions. ..
  30. CONSTRUCTION OF AN ANTIBODY ENGINEERING LABORATORY
    David Gold; Fiscal Year: 1999
    ..Antibody Engineering Laboratory Program for the research and development of monoclonal antibodies, immunoconjugates, and related derivatives in support of CMMI's clinical trials...
  31. Ag(111) Carbeneporphyrinoids as Radiopharmaceuticals
    WILEY YOUNGS; Fiscal Year: 2002
    ..The sixth objective of this proposal will be to determine toxicity, clearance, and the effectiveness of the targeted metallocarbeneporphyrinoid in reducing carcinoma in small animals. ..
  32. TARGETING THE VASCULATURE OF SOLID TUMORS
    Philip Thorpe; Fiscal Year: 1999
    DESCRIPTION: (Applicant's Abstract) The goal of this application is to create immunoconjugates that home to the vasculature of solid tumors, coagulate the tumor's blood supply and induce tumor infarction...
  33. BISPECIFIC ANTIBODY FOR DIRECTED DELIVERY OF PALYTOXIN
    Gary Bignami; Fiscal Year: 1991
    ..Abstract) Considerable interest has been focussed on the production and characterization of therapeutic immunoconjugates. Such hybrid molecules usually consist of a monoclonal antibody with covalently attached toxin, drug, or ..
  34. HIGH-DOSE RADIOIMMUNOTHERAPY FOR BREAST CANCER
    Pablo Cagnoni; Fiscal Year: 1999
    ..In addition, we will study the dosimetry and pharmacokinetics of the radiolabel and we will also obtain preliminary estimates of its efficacy in preparation for a phase II study in the future. ..
  35. RANDOM SINGLE CHAIN ANTIBODY LIBRARY
    JAMES LARRICK; Fiscal Year: 1992
    ..Many therapeutic and diagnostic applications are apparent, including infectious diseases, cancer, immunoconjugates and catalytic antibodies.
  36. Mechanisms of Resistance to Gemtuzumab Ozogamicin
    Irwin Bernstein; Fiscal Year: 2006
    ..In phase I and II clinical trials, we will determine whether CSA can enhance the therapeutic effectiveness of GO in patients with relapsed AML (Aim III). ..
  37. T CELL RECEPTOR-BASED IMMUNOTHERAPEUTICS FOR CANCER
    Hing Wong; Fiscal Year: 2001
    ..proposed commercial application: not available ..
  38. Laser photothermolysis of scar in vocal cords
    Elie Rebeiz; Fiscal Year: 2002
    ..This immunoconjugate assisted laser minimally invasive therapy, if success, will certainly provide an excellent alternative to current therapy in the prevention and treatment of hypertrophic scar formation. ..
  39. Targeting Metastatic Breast Cancer with Human Antibodies
    Brunhilde Felding Habermann; Fiscal Year: 2009
    ..Novel immunoconjugates containing small, highly toxic compounds will be tested for their effects on metastatic breast cancer...
  40. EXPERIMENTAL PHOTOIMMUNOTHERAPY OF OVARIAN CANCER
    Tayyaba Hasan; Fiscal Year: 2006
    ..The systemic toxicity associated with radio- and chemo-immunoconjugates may thus be significantly reduced in PIT due to the dual selectivity provided by the tumor localizing ability ..
  41. Conference on Antibody-Based Therapeutics for Cancer
    Louis Weiner; Fiscal Year: 2004
    ..This meeting will address these challenges in distinct sessions devoted to antibody structure and function, immunoconjugates, antibodies as tools for target discovery, antibodies as signaling agents and immune effectors, and in a ..
  42. CC-1065 ANALOGS--IDEAL DRUGS FOR ANTICANCER CONJUGATES
    Ravi Chari; Fiscal Year: 1993
    Currently used anti-cancer agents have limited selectivity for the tumor. Immunoconjugates that have been prepared from these drugs are not potent enough to be therapeutically effective...
  43. 5TH INTERNATIONAL CONFERENCE ON MOAB IMMUNOCONJUGATES
    Ivor Royston; Fiscal Year: 1990
    ..This conference continues to focus on the major developments in the field of monoclonal antibody conjugates for clinical use in cancer...
  44. CONF ON MONOCLONAL ANTIBODY IMMUNOCONJUGATES FOR CANCER
    Ivor Royston; Fiscal Year: 1991
    ..This conference continues to focus on the major developments in the field of monoclonal antibody conjugates for clinical use in cancer...
  45. INNOVATIVE TARGETED APPROACHES TO CMV INFECTIONS
    Steven Foung; Fiscal Year: 1991
    ..3) Production and functional characterization of immunoconjugates with different classes of reagents (selective complement activators, toxins, and anti-viral drugs) for ..
  46. REAGENTS FOR IDENTIFICATION OF ANTIGEN-SPECIFIC T CELLS
    Michael Anderson; Fiscal Year: 2000
    ..C (I-Ek/d- MCCO linked to a pentameric platform of cholera toxin-B (CT-B) subunits is proposed to develop immunoconjugates for direct detection of antigen- specific T cells...
  47. CONFERENCE--MAB IMMUNOCONJUGATES FOR CANCER
    Ivor Royston; Fiscal Year: 1992
    ..This conference continues to focus on the major developments in the field of monoclonal antibodies for clinical use in cancer...
  48. BIOLOGICAL APPROACHES TO AIDS LYMPHOMA
    David Scadden; Fiscal Year: 1993
    ..In addition, these phenomena may lend themselves to the development of therapeutic agents due to their involvement of cell surface structures potentially accessible to cytokine or adhesion based therapeutics...
  49. TARGETED PRODRUGS OF 9-AMINOCAMPTOTHECIN
    SEAN O MALLEY; Fiscal Year: 2001
    ..A clinically effective 9-aminocamptothecin prodrug would have significant commercial value as a pharmaceutical product. ..
  50. Antibody-Based Therapeutics for Cancer
    Louis Weiner; Fiscal Year: 2003
    ..This meeting will address these challenges in distinct sessions devoted to antibody structure and function, immunoconjugates, antibodies as tools for target discovery, antibodies as signaling agents and immune effectors, and in a ..
  51. DEVELOPMENT OF BREAST-SPECIFIC ANTIBODIES
    Candace Swimmer; Fiscal Year: 1993
    ..Expression of this library in a murine cell line will create a novel set of antigens that should upon immunization lead to antibodies with the desired breast tumor restricted specificity...
  52. CONFERENCE ON MONOCLONAL ANTIBODIES
    Charles Fox; Fiscal Year: 1991
    ..at this conference will address issues in the areas of binding sites, effector mechanisms, surface receptor molecules, immunoconjugates, protein design, clinical trials, animal models, and other issues that impact on these strategies.
  53. RAIT of Pancreatic Cancer with Humanized PAM4
    ROBERT SHARKEY; Fiscal Year: 2005
    ..The trial will be conducted at the Garden State Cancer Center and Johns Hopkins University School of Medicine. CMMI will be responsible for monitoring the study's progress. ..
  54. Improved Detection of Cancer Using Bi Specific Antibody
    ROBERT SHARKEY; Fiscal Year: 2002
    ....
  55. Improved Detection of Cancer Using Bi Specific Antibody
    ROBERT SHARKEY; Fiscal Year: 2003
    ....
  56. Bispecific Antibody Pretargeted Therapy of Pancreatic Cancer
    ROBERT SHARKEY; Fiscal Year: 2008
    ..Overall, these studies will assist in establishing whether this type of pretargeting approach could have a role in the clinical management of pancreatic cancer. [unreadable] [unreadable] [unreadable]..
  57. Bispecific Antibody Pretargeting for Therapy
    ROBERT SHARKEY; Fiscal Year: 2009
    ..Anti-antibody responses will also be measured to the humanized bsMAb. This clinical trial will be conducted at the Fox Chase Cancer Center. ..
  58. Doxorubicin-Immunoconjugate Therapy of Non-Hodgkin's Lymphoma
    Rhona Stein; Fiscal Year: 2008
    ..abstract_text> ..
  59. Fullerene Immunoconjugates for Cancer Imaging and Treatment
    ROBERT BOLSKAR; Fiscal Year: 2008
    ..Using the Gd@C60-paclitaxel conjugates, new immunoconjugates with the anti-gp240 melanoma antibody ZME-018 will be formed and tested for cellular uptake, for MRI contrast ..