Thomas A Waldmann

Summary

Affiliation: National Institutes of Health
Country: USA

Publications

  1. pmc Targeting the interleukin-15/interleukin-15 receptor system in inflammatory autoimmune diseases
    Thomas A Waldmann
    Metabolism Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA
    Arthritis Res Ther 6:174-7. 2004
  2. pmc Effective therapy for a murine model of human anaplastic large-cell lymphoma with the anti-CD30 monoclonal antibody, HeFi-1, does not require activating Fc receptors
    Meili Zhang
    Metabolism Branch, Radiation Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA
    Blood 108:705-10. 2006
  3. ncbi request reprint Pretargeted alpha emitting radioimmunotherapy using (213)Bi 1,4,7,10-tetraazacyclododecane-N,N',N",N"'-tetraacetic acid-biotin
    Zhengsheng Yao
    Department of Nuclear Medicine, Warren G Magnuson Clinical Center, NIH, Bethesda, Maryland 20892, USA
    Clin Cancer Res 10:3137-46. 2004
  4. pmc Preclinical evaluation of an anti-CD25 monoclonal antibody, 7G7/B6, armed with the beta-emitter, yttrium-90, as a radioimmunotherapeutic agent for treating lymphoma
    Meili Zhang
    Metabolism Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892 1374, USA
    Cancer Biother Radiopharm 24:303-9. 2009
  5. ncbi request reprint Preparation and in vivo evaluation of a novel stabilized linker for 211At labeling of protein
    Vladimir S Talanov
    Radiation Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA
    Nucl Med Biol 33:469-80. 2006
  6. ncbi request reprint Activating Fc receptors are required for antitumor efficacy of the antibodies directed toward CD25 in a murine model of adult t-cell leukemia
    Meili Zhang
    Metabolism Branch, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland 20892 1374, USA
    Cancer Res 64:5825-9. 2004
  7. pmc Interleukin-15 and its receptor augment dendritic cell vaccination against the neu oncogene through the induction of antibodies partially independent of CD4 help
    Jason C Steel
    Metabolism Branch, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland 20892 1374, USA
    Cancer Res 70:1072-81. 2010
  8. pmc Effective treatment of a murine model of adult T-cell leukemia using depsipeptide and its combination with unmodified daclizumab directed toward CD25
    Jing Chen
    Metabolism Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA
    Blood 113:1287-93. 2009
  9. pmc Effective treatment of a murine model of adult T-cell leukemia using 211At-7G7/B6 and its combination with unmodified anti-Tac (daclizumab) directed toward CD25
    Zhuo Zhang
    Metabolism Branch, NCI, NIH, Bldg 10, Room 4N115, 10 Center Drive, Bethesda, MD 20892 1374, USA
    Blood 108:1007-12. 2006
  10. pmc Effective therapy of murine models of human leukemia and lymphoma with radiolabeled anti-CD30 antibody, HeFi-1
    Meili Zhang
    Metabolism Branch, Center for Cancer Research, National Cancer Institute, PET Department, Clinical Center, National Institutes of Health, Bethesda, MD 20892, USA
    Proc Natl Acad Sci U S A 104:8444-8. 2007

Collaborators

Detail Information

Publications91

  1. pmc Targeting the interleukin-15/interleukin-15 receptor system in inflammatory autoimmune diseases
    Thomas A Waldmann
    Metabolism Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA
    Arthritis Res Ther 6:174-7. 2004
    ....
  2. pmc Effective therapy for a murine model of human anaplastic large-cell lymphoma with the anti-CD30 monoclonal antibody, HeFi-1, does not require activating Fc receptors
    Meili Zhang
    Metabolism Branch, Radiation Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA
    Blood 108:705-10. 2006
    ..We demonstrated that the expression of FcRgamma on polymorphonuclear leukocytes and monocytes was not required for HeFi-1-mediated tumor growth inhibition in vivo, although it was required for daclizumab...
  3. ncbi request reprint Pretargeted alpha emitting radioimmunotherapy using (213)Bi 1,4,7,10-tetraazacyclododecane-N,N',N",N"'-tetraacetic acid-biotin
    Zhengsheng Yao
    Department of Nuclear Medicine, Warren G Magnuson Clinical Center, NIH, Bethesda, Maryland 20892, USA
    Clin Cancer Res 10:3137-46. 2004
    ..This study investigated the biodistribution of bismuth-labeled biotin in A431 tumor-bearing mice pretargeted with antibody B3-streptavidin (B3-SA) and examined the therapeutic efficacy of the alpha emitter, (213)Bi-labeled biotin...
  4. pmc Preclinical evaluation of an anti-CD25 monoclonal antibody, 7G7/B6, armed with the beta-emitter, yttrium-90, as a radioimmunotherapeutic agent for treating lymphoma
    Meili Zhang
    Metabolism Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892 1374, USA
    Cancer Biother Radiopharm 24:303-9. 2009
    ..Radioimmunotherapy of cancer with radiolabeled antibodies has shown promise. We evaluated an anti-CD25 monoclonal Antibody, 7G7/B6, armed with (90)Y as a potential radioimmunotherapeutic agent for CD25-expressing lymphomas...
  5. ncbi request reprint Preparation and in vivo evaluation of a novel stabilized linker for 211At labeling of protein
    Vladimir S Talanov
    Radiation Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA
    Nucl Med Biol 33:469-80. 2006
    ..The in vivo studies also revealed that the N-methyl modification resulted in a superior statinated product...
  6. ncbi request reprint Activating Fc receptors are required for antitumor efficacy of the antibodies directed toward CD25 in a murine model of adult t-cell leukemia
    Meili Zhang
    Metabolism Branch, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland 20892 1374, USA
    Cancer Res 64:5825-9. 2004
    ..Although NK cells may play a role in humans, in this murine model FcRgamma receptors on non-NK cells, such as polymorphonuclear leukocytes or monocytes, are required for the tumor-killing action of the antibodies directed toward CD25...
  7. pmc Interleukin-15 and its receptor augment dendritic cell vaccination against the neu oncogene through the induction of antibodies partially independent of CD4 help
    Jason C Steel
    Metabolism Branch, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland 20892 1374, USA
    Cancer Res 70:1072-81. 2010
    ..Coexpression of IL-15 and IL-15Ralpha in an anticancer vaccine enhanced immune responses against the NEU antigen and may overcome impaired CD4(+) T-helper function...
  8. pmc Effective treatment of a murine model of adult T-cell leukemia using depsipeptide and its combination with unmodified daclizumab directed toward CD25
    Jing Chen
    Metabolism Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA
    Blood 113:1287-93. 2009
    ..001). The significantly improved therapeutic efficacy by combining depsipeptide with daclizumab supports a clinical trial of this combination in the treatment of ATL...
  9. pmc Effective treatment of a murine model of adult T-cell leukemia using 211At-7G7/B6 and its combination with unmodified anti-Tac (daclizumab) directed toward CD25
    Zhuo Zhang
    Metabolism Branch, NCI, NIH, Bldg 10, Room 4N115, 10 Center Drive, Bethesda, MD 20892 1374, USA
    Blood 108:1007-12. 2006
    ..These results that demonstrate a significantly improved therapeutic efficacy by combining (211)At-7G7/B6 with daclizumab support a clinical trial of this regimen in patients with ATL...
  10. pmc Effective therapy of murine models of human leukemia and lymphoma with radiolabeled anti-CD30 antibody, HeFi-1
    Meili Zhang
    Metabolism Branch, Center for Cancer Research, National Cancer Institute, PET Department, Clinical Center, National Institutes of Health, Bethesda, MD 20892, USA
    Proc Natl Acad Sci U S A 104:8444-8. 2007
    ..001). In summary, radiolabeled HeFi-1 is very promising for the treatment of CD30-expressing leukemias and lymphomas, and the combination regimen of (211)At-HeFi-1 with unmodified HeFi-1 enhanced the therapeutic efficacy...
  11. ncbi request reprint Comparison of dendrimer-based macromolecular contrast agents for dynamic micro-magnetic resonance lymphangiography
    Hisataka Kobayashi
    Metabolism Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892 1374, USA
    Magn Reson Med 50:758-66. 2003
    ..In conclusion, DAB-G5 and PAMAM-G4 can be used to identify lymph nodes and lymphatic vessels, respectively. Their rapid excretion makes these compounds potentially attractive for human use...
  12. ncbi request reprint Role of trans-cellular IL-15 presentation in the activation of NK cell-mediated killing, which leads to enhanced tumor immunosurveillance
    Hisataka Kobayashi
    Metabolism Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA
    Blood 105:721-7. 2005
    ..Furthermore, our observation provides the scientific basis for a novel strategy to prevent cancer development/metastasis...
  13. ncbi request reprint Preassociation of IL-15 with IL-15R alpha-IgG1-Fc enhances its activity on proliferation of NK and CD8+/CD44high T cells and its antitumor action
    Sigrid Dubois
    Metabolism Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, 10 Center Drive, Bethesda, MD 20892, USA
    J Immunol 180:2099-106. 2008
    ..Thus, a preassociation with IL-15Ralpha-IgG1-Fc enhances the activities of IL-15 in vivo and in vitro that may be useful in the treatment of tumors...
  14. pmc Regulatory CD56(bright) natural killer cells mediate immunomodulatory effects of IL-2Ralpha-targeted therapy (daclizumab) in multiple sclerosis
    Bibiana Bielekova
    Neuroimmunology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892, USA
    Proc Natl Acad Sci U S A 103:5941-6. 2006
    ..This immunoregulation has potential importance for the treatment of autoimmune diseases and transplant rejection and toward modification of tumor immunity...
  15. pmc Effect of anti-CD25 antibody daclizumab in the inhibition of inflammation and stabilization of disease progression in multiple sclerosis
    Bibiana Bielekova
    Neuroimmunology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bldg 10, Room 5C103, 10 Center Dr, MSC 1400, Bethesda, MD 20892, USA
    Arch Neurol 66:483-9. 2009
    ..Several questions arise concerning the use of the anti-CD25 antibody daclizumab to treat multiple sclerosis (MS)...
  16. pmc Interleukin-15 combined with an anti-CD40 antibody provides enhanced therapeutic efficacy for murine models of colon cancer
    Meili Zhang
    Metabolism Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA
    Proc Natl Acad Sci U S A 106:7513-8. 2009
    ..The findings from this study provide the scientific basis for clinical trials using the combination regimen of IL-15 with an anti-CD40 antibody for the treatment of patients with cancer...
  17. ncbi request reprint Preparation and in vivo evaluation of novel linkers for 211At labeling of proteins
    Vladimir S Talanov
    Radiation Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA
    Nucl Med Biol 31:1061-71. 2004
    ..Formation of 11, however, is found to require the absence of NCS. Elimination of acetic acid is found to have no effect on radiolabeling efficiency or yield for either of these reactions...
  18. pmc Transient and persistent effects of IL-15 on lymphocyte homeostasis in nonhuman primates
    Enrico Lugli
    Immunotechnology Section, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health NIH, Bethesda, MD, USA
    Blood 116:3238-48. 2010
    ..Thus, IL-15 generates a dramatic expansion of short-lived memory CD8 T cells and NK cells in immunocompetent macaques and has long-term effects on the balance of CD4(+) and CD8(+) T cells...
  19. pmc IL-15 as a mediator of CD4+ help for CD8+ T cell longevity and avoidance of TRAIL-mediated apoptosis
    SangKon Oh
    Vaccine Branch and Metabolism Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892 1578, USA
    Proc Natl Acad Sci U S A 105:5201-6. 2008
    ..These findings suggest new vaccine strategies against infections and cancers, especially in individuals with CD4-deficiency...
  20. ncbi request reprint The anti-CD25 monoclonal antibody 7G7/B6, armed with the alpha-emitter 211At, provides effective radioimmunotherapy for a murine model of leukemia
    Meili Zhang
    Metabolism Branch, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD 20892 1374, USA
    Cancer Res 66:8227-32. 2006
    ..In summary, (211)At-7G7/B6 could serve as an effective therapeutic agent for patients with CD25-expressing leukemias...
  21. ncbi request reprint Lymphatic drainage imaging of breast cancer in mice by micro-magnetic resonance lymphangiography using a nano-size paramagnetic contrast agent
    Hisataka Kobayashi
    Metabolism Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892 1374, USA
    J Natl Cancer Inst 96:703-8. 2004
    ..Improving current magnetic resonance (MR) imaging methods using a newly synthesized nano-size paramagnetic molecule, G6, as a contrast agent, provides an attractive means toward attaining this goal...
  22. pmc Central memory self/tumor-reactive CD8+ T cells confer superior antitumor immunity compared with effector memory T cells
    Christopher A Klebanoff
    Howard Hughes Medical Institute, National Institutes of Health Research Scholars Program, Bethesda, MD 20814, USA
    Proc Natl Acad Sci U S A 102:9571-6. 2005
    ..Thus, tumor-reactive CD8+ T cell populations with the phenotypic and functional attributes of T(CM) may be superior to T(EM)/effector T cells for adoptive immunotherapies using concomitant tumor-antigen vaccination...
  23. pmc IL-15/IL-15Ralpha-mediated avidity maturation of memory CD8+ T cells
    SangKon Oh
    Vaccine Branch and Metabolism Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA
    Proc Natl Acad Sci U S A 101:15154-9. 2004
    ..Conversely, high-avidity CTLs are diminished in IL-15Ralpha knockout mice. These results provide an explanation of CD8+ T cell avidity maturation and may contribute to the design of novel vaccines...
  24. pmc IL-15 expands unconventional CD8alphaalphaNK1.1+ T cells but not Valpha14Jalpha18+ NKT cells
    Masaki Terabe
    Vaccine Branch, National Cancer Institute, National Institute of Health, Bethesda, MD 20893, USA
    J Immunol 180:7276-86. 2008
    ..1(+) T cell subset, CD8alphaalphaNK1.1(+) T cells, and that IL-15-transgenic mice may be a useful resource for studying the functional relevance of CD8(+)NK1.1(+) T cells...
  25. pmc Safety (toxicity), pharmacokinetics, immunogenicity, and impact on elements of the normal immune system of recombinant human IL-15 in rhesus macaques
    Thomas A Waldmann
    Center for Cancer Research, National Cancer Institute, Frederick, MD, USA
    Blood 117:4787-95. 2011
    ....
  26. pmc The IL-15/IL-15Ralpha on cell surfaces enables sustained IL-15 activity and contributes to the long survival of CD8 memory T cells
    Noriko Sato
    Metabolism Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA
    Proc Natl Acad Sci U S A 104:588-93. 2007
    ....
  27. pmc Detection of lymph node involvement in hematologic malignancies using micromagnetic resonance lymphangiography with a gadolinum-labeled dendrimer nanoparticle
    Hisataka Kobayashi
    Molecular Imaging Program, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892 1088, USA
    Neoplasia 7:984-91. 2005
    ....
  28. pmc Gene expression profiling of ATL patients: compilation of disease-related genes and evidence for TCF4 involvement in BIRC5 gene expression and cell viability
    Cynthia A Pise-Masison
    Laboratory of Cellular Oncology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA
    Blood 113:4016-26. 2009
    ..These experiments represent the first direct experimental evidence that BIRC5 plays an important role in ATL cell viability and provides important insight into ATL genesis and potential targeted therapies...
  29. ncbi request reprint Herceptin-geldanamycin immunoconjugates: pharmacokinetics, biodistribution, and enhanced antitumor activity
    Raya Mandler
    Metabolism Branch, Center for Cancer Research, National Cancer Institute NIH, 6701 Rockledge Drive, Room 5217, MSC 7840, Bethesda, MD 20892, USA
    Cancer Res 64:1460-7. 2004
    ..In addition, the chemical linkage and the considerations in therapeutic regimen described here could be applied to other immunoconjugates for targeted therapy of a broad spectrum of cancers...
  30. pmc Autocrine/paracrine cytokine stimulation of leukemic cell proliferation in smoldering and chronic adult T-cell leukemia
    Jing Chen
    Metabolism Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892 1374, USA
    Blood 116:5948-56. 2010
    ..In conclusion, our data provide evidence that there is autocrine/paracrine cytokine stimulation of leukemic cell proliferation in patients with smoldering/chronic ATL that could be targeted for treatment...
  31. ncbi request reprint Radioimmunotherapy of A431 xenografted mice with pretargeted B3 antibody-streptavidin and (90)Y-labeled 1,4,7,10-tetraazacyclododecane-N,N',N",N"'-tetraacetic acid (DOTA)-biotin
    Zhengsheng Yao
    Nuclear Medicine Department of the Warren G Magnuson Clinical Center, National Cancer Institute, NIH, Bethesda, Maryland 20892, USA
    Cancer Res 62:5755-60. 2002
    ....
  32. pmc Augmented IL-15Rα expression by CD40 activation is critical in synergistic CD8 T cell-mediated antitumor activity of anti-CD40 antibody with IL-15 in TRAMP-C2 tumors in mice
    Meili Zhang
    Metabolism Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA
    J Immunol 188:6156-64. 2012
    ..These findings support the view that anti-CD40-mediated augmented IL-15Rα expression was critical in IL-15-associated sustained remissions observed in TRAMP-C2 tumor-bearing mice receiving combination therapy...
  33. pmc ITK and IL-15 support two distinct subsets of CD8+ T cells
    Sigrid Dubois
    Metabolism Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA
    Proc Natl Acad Sci U S A 103:12075-80. 2006
    ..Thus, whereas ITK-dependent CD44(lo)CD122(lo) CD8(+) T cells appear to represent conventional CD8(+) T cells, IL-15-dependent CD44(hi)CD122(hi) CD8(+) T cells may have functions in both adaptive and innate immunity...
  34. ncbi request reprint Combination therapy for adult T-cell leukemia-xenografted mice: flavopiridol and anti-CD25 monoclonal antibody
    Meili Zhang
    Metabolism Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bldg 10, Rm 4N115, 10 Center Dr, Bethesda, MD 20892, USA
    Blood 105:1231-6. 2005
    ..01). The significantly improved therapeutic efficacy by combining flavopiridol with HAT provides support for a clinical trial in the treatment of ATL...
  35. pmc CP-690,550, a therapeutic agent, inhibits cytokine-mediated Jak3 activation and proliferation of T cells from patients with ATL and HAM/TSP
    Wei Ju
    Metabolism Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health NIH, Bethesda, MD 20892 1374, USA
    Blood 117:1938-46. 2011
    ..These studies support further evaluation of the Jak3 inhibitor CP-690,550 in the treatment of select patients with HTLV-I-associated ATL and HAM/TSP...
  36. ncbi request reprint A pilot study of CTLA-4 blockade after cancer vaccine failure in patients with advanced malignancy
    John C Morris
    Metabolism Branch, Laboratory of Pathology, Department of Laboratory Medicine, National Eye Institute, Bethesda, MD 20892 1457, USA
    Clin Cancer Res 13:958-64. 2007
    ..The primary end point was to determine drug toxicity. Tumor response, tumor-specific CD8+ T-cell immune responses, and modulation of CD4+ CD25+ FoxP3+ regulatory T-cell (Treg) numbers were secondary end points...
  37. pmc Pretarget radiotherapy with an anti-CD25 antibody-streptavidin fusion protein was effective in therapy of leukemia/lymphoma xenografts
    Meili Zhang
    Metabolism and Radiation Oncology Branches, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892 1374, USA
    Proc Natl Acad Sci U S A 100:1891-5. 2003
    ..Thus, Pretarget radioimmunotherapy is very promising and could represent the next generation in the treatment of lymphoma and leukemia...
  38. pmc Markedly additive antitumor activity with the combination of a selective survivin suppressant YM155 and alemtuzumab in adult T-cell leukemia
    Jing Chen
    Metabolism Branch, National Cancer Institute, Bethesda, MD 20892, USA
    Blood 121:2029-37. 2013
    ..Our data support a clinical trial of the combination of YM155 with alemtuzumab in ATL. This trial was registered at www.clinicaltrials.gov as #NCT00061048...
  39. pmc Simultaneous inhibition of two regulatory T-cell subsets enhanced Interleukin-15 efficacy in a prostate tumor model
    Ping Yu
    Metabolism Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA
    Proc Natl Acad Sci U S A 109:6187-92. 2012
    ..Combining the immune stimulatory properties of IL-15 with simultaneous removal of two critical immune inhibitory checkpoints, we showed enhancement of immune responses, leading to increased antitumor activity...
  40. ncbi request reprint Anti-Tac (daclizumab, Zenapax) in the treatment of leukemia, autoimmune diseases, and in the prevention of allograft rejection: a 25-year personal odyssey
    Thomas A Waldmann
    Metabolism Branch, Center for Cancer Research, National Cancer Institute, NIH Building 10, Bethesda, Maryland 20892 1374, USA
    J Clin Immunol 27:1-18. 2007
    ....
  41. pmc IL-15 serves as a costimulator in determining the activity of autoreactive CD8 T cells in an experimental mouse model of graft-versus-host-like disease
    Fumi Miyagawa
    Dermatology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA
    J Immunol 181:1109-19. 2008
    ....
  42. pmc Development of an IL-15-autocrine CD8 T-cell leukemia in IL-15-transgenic mice requires the cis expression of IL-15Rα
    Noriko Sato
    Metabolism Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA
    Blood 117:4032-40. 2011
    ....
  43. pmc Survival adjustment of mature dendritic cells by IL-15
    Sigrid P Dubois
    Metabolism Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA
    Proc Natl Acad Sci U S A 102:8662-7. 2005
    ..These findings support the hypothesis that DCs mediate the effect of IL-15 on CD8+/CD44(hi) memory phenotype T cells...
  44. pmc Simultaneous blockade of multiple immune system inhibitory checkpoints enhances antitumor activity mediated by interleukin-15 in a murine metastatic colon carcinoma model
    Ping Yu
    Metabolism Branch, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland 20892, USA
    Clin Cancer Res 16:6019-28. 2010
    ..Its effectiveness, however, may be limited by inhibitory checkpoints and pathways that can attenuate immune responses. Finding strategies to abrogate these negative regulators and enhance the efficacy of IL-15 is a critical challenge...
  45. pmc Induction of the IL-9 gene by HTLV-I Tax stimulates the spontaneous proliferation of primary adult T-cell leukemia cells by a paracrine mechanism
    Jing Chen
    Metabolism Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA
    Blood 111:5163-72. 2008
    ..In summary, these data support a role for IL-9 and its receptor in ATL by a paracrine mechanism...
  46. pmc Preclinical and phase I clinical trial of blockade of IL-15 using Mikbeta1 monoclonal antibody in T cell large granular lymphocyte leukemia
    John C Morris
    Metabolism Branch, Center for Cancer Research, and Office of Cancer Complementary and Alternative Medicine, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA
    Proc Natl Acad Sci U S A 103:401-6. 2006
    ....
  47. pmc Paracrine and transpresentation functions of IL-15 are mediated by diverse splice versions of IL-15Rα in human monocytes and dendritic cells
    Jürgen R Müller
    Metabolism Branch, NCI, National Institutes of Health, Bethesda, MD 20892, USA
    J Biol Chem 287:40328-38. 2012
    ..IL-15 can either be transpresented by IL-15Rα or be secreted...
  48. pmc Selective dependence of H2-M3-restricted CD8 responses on IL-15
    Jürgen R Müller
    Metabolism Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA
    J Immunol 188:2575-82. 2012
    ..These data suggest that the nature of the selecting MHC class Ib molecule determines whether CD8(+) T cells acquire IL-15 dependence during thymic development...
  49. pmc Increased serum soluble IL-15Rα levels in T-cell large granular lymphocyte leukemia
    Jing Chen
    Metabolism Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892 1374, USA
    Blood 119:137-43. 2012
    ..It is conceivable that higher IL-15Rα expression may lower IL-15 response threshold in vivo and, therefore, may contribute to the pathogenesis of the disease...
  50. pmc Exploiting synthetic lethality for the therapy of ABC diffuse large B cell lymphoma
    Yibin Yang
    Metabolism Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA
    Cancer Cell 21:723-37. 2012
    ..Blockade of B cell receptor signaling using the BTK inhibitor ibrutinib also downregulates IRF4 and consequently synergizes with lenalidomide in killing ABC DLBCLs, suggesting attractive therapeutic strategies...
  51. ncbi request reprint Application of a macromolecular contrast agent for detection of alterations of tumor vessel permeability induced by radiation
    Hisataka Kobayashi
    Metabolism Branch, Radiation Biology Branch, and Radiation Oncology Branch, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland 20892 1002, USA
    Clin Cancer Res 10:7712-20. 2004
    ..Such information might be applied to optimize the efficacy of subsequent or concurrent therapies including radiolabeled antibodies or other anticancer agents in combination with external beam therapies...
  52. pmc Highly persistent and effective prime/boost regimens against tuberculosis that use a multivalent modified vaccine virus Ankara-based tuberculosis vaccine with interleukin-15 as a molecular adjuvant
    Kristopher Kolibab
    Laboratory of Mycobacterial Diseases and Cellular Immunology, Center for Biologics Evaluation and Research, U S Food and Drug Administration, Bethesda, MD 20892, USA
    Clin Vaccine Immunol 17:793-801. 2010
    ....
  53. pmc A role for interleukin-2 trans-presentation in dendritic cell-mediated T cell activation in humans, as revealed by daclizumab therapy
    Simone C Wuest
    Neuroimmunology Branch, National Institute of Neurological Disorders and Stroke NINDS, National Institutes of Health NIH, Bethesda, Maryland, USA
    Nat Med 17:604-9. 2011
    ..Our data reveal a previously unknown mechanism for the IL-2 receptor system in DC-mediated activation of T cells...
  54. pmc Augmented efficacy of brentuximab vedotin combined with ruxolitinib and/or Navitoclax in a murine model of human Hodgkin's lymphoma
    Wei Ju
    Lymphoid Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892
    Proc Natl Acad Sci U S A 113:1624-9. 2016
    ..These studies provide scientific support for a clinical trial to evaluate BV combined with ruxolitinib in select patients with HL. ..
  55. ncbi request reprint Systemic radioimmunotherapy using a monoclonal antibody, anti-Tac directed toward the alpha subunit of the IL-2 receptor armed with the alpha-emitting radionuclides (212)Bi or (211)At
    Jon N Wesley
    Metabolism Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA
    Nucl Med Biol 31:357-64. 2004
    ..7+/-2.4 days survival (p<0.001 versus controls) with (211)At labeled HAT. Thus, (211)At labeled HAT may have application in organ transplantation and in treatment of IL-2 receptor expressing T-cell leukemia...
  56. ncbi request reprint Micro-MRI methods to detect renal cysts in mice
    Hisataka Kobayashi
    Metabolism Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA
    Kidney Int 65:1511-6. 2004
    ....
  57. ncbi request reprint Effective therapy for a murine model of adult T-cell leukemia with the humanized anti-CD52 monoclonal antibody, Campath-1H
    Zhuo Zhang
    Metabolism Branch, Center for Cancer Research, National Cancer Institute NIH, Building 10, Room 4N115, 10 Center Drive, Bethesda, MD 20892 1374, USA
    Cancer Res 63:6453-7. 2003
    ..This study provides support for a clinical trial of Campath-1H in the treatment of patients with T-cell leukemias and lymphomas...
  58. pmc Burkitt lymphoma pathogenesis and therapeutic targets from structural and functional genomics
    Roland Schmitz
    Metabolism Branch Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland 20892, USA
    Nature 490:116-20. 2012
    ..In 38% of sporadic BL cases, oncogenic CCND3 mutations produced highly stable cyclin D3 isoforms that drive cell cycle progression. These findings suggest opportunities to improve therapy for patients with BL...
  59. ncbi request reprint IL-15 in the life and death of lymphocytes: immunotherapeutic implications
    Thomas A Waldmann
    Metabolism Branch, Center for Cancer Research, National Cancer Institute National Institutes of Health, Bethesda, MD 20892 1374, USA
    Trends Mol Med 9:517-21. 2003
  60. pmc Distinct pathways involving the FK506-binding proteins 12 and 12.6 underlie IL-2-versus IL-15-mediated proliferation of T cells
    Sigrid Dubois
    Metabolism Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA
    Proc Natl Acad Sci U S A 100:14169-74. 2003
    ..Thus, IL-15 induces T cell proliferation mainly via FKBP12-mediated p70S6K activation. In contrast, IL-2 signaling involves multiple pathways that include at least one additional pathway that depends on FKBP12.6...
  61. pmc Smallpox vaccine with integrated IL-15 demonstrates enhanced in vivo viral clearance in immunodeficient mice and confers long term protection against a lethal monkeypox challenge in cynomolgus monkeys
    Rafal J Zielinski
    Radiation Oncology Branch, National Cancer Institute, Bethesda, MD 20892 1374, USA
    Vaccine 28:7081-91. 2010
    ....
  62. doi request reprint Receptor-directed therapy of T-cell leukemias and lymphomas
    John C Morris
    Metabolism Branch, Center for Cancer Research, National Cancer Institute, Mark O Hatfield Clinical Research Center, Bethesda, Maryland 20892 1457, USA
    J Immunotoxicol 5:235-48. 2008
    ..The current status of receptor-directed antibody therapy for T-cell leukemia and lymphoma is reviewed...
  63. pmc Development of a highly efficacious vaccinia-based dual vaccine against smallpox and anthrax, two important bioterror entities
    Tod J Merkel
    Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, MD 20892, USA
    Proc Natl Acad Sci U S A 107:18091-6. 2010
    ....
  64. ncbi request reprint Effective therapy for a murine model of adult T-cell leukemia with the humanized anti-CD2 monoclonal antibody, MEDI-507
    Zhuo Zhang
    Metabolism Branch, Center for Cancer Research, National Cancer Institute NIH, Bldg 10, Rm 4N115, 10 Center Drive, Bethesda, MD 20892 1374, USA
    Blood 102:284-8. 2003
    ..These results demonstrate that MEDI-507 has therapeutic efficacy on ATL in vivo and provides support for a clinical trial involving this monoclonal antibody in the treatment of patients with CD2-expressing leukemias and lymphomas...
  65. pmc Coadministration of HIV vaccine vectors with vaccinia viruses expressing IL-15 but not IL-2 induces long-lasting cellular immunity
    SangKon Oh
    Molecular Immunogenetics and Vaccine Research Section, Metabolism Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA
    Proc Natl Acad Sci U S A 100:3392-7. 2003
    ....
  66. pmc A new domain in the Toll/IL-1R domain-containing adaptor inducing interferon-β factor protein amino terminus is important for tumor necrosis factor-α receptor-associated factor 3 association, protein stabilization and interferon signaling
    Vinh Phuc Nguyen
    Metabolism Branch, Center for Cancer Research, National Institutes of Health, Bethesda, MD, USA
    J Innate Immun 6:377-93. 2014
    ..Therefore, this 21 amino acid sequence is crucial for TRAF3 association, modulation of TRIF stability and activation of the IFN pathway...
  67. ncbi request reprint Immunotherapy: past, present and future
    Thomas A Waldmann
    Metabolism Branch, Center for Cancer Research National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA
    Nat Med 9:269-77. 2003
  68. ncbi request reprint Humanized anti-interleukin-2 (IL-2) receptor alpha therapy: long-term results in uveitis patients and preliminary safety and activity data for establishing parameters for subcutaneous administration
    Robert B Nussenblatt
    The National Eye Institute, Laboratory of Immunology, NIH, Building 10, 10 Center Drive, Bethesda, MD, USA
    J Autoimmun 21:283-93. 2003
    ..These studies suggest that anti-IL-2 receptor blockade could be useful in the treatment of Th1-mediated autoimmune conditions...
  69. ncbi request reprint The biology of interleukin-2 and interleukin-15: implications for cancer therapy and vaccine design
    Thomas A Waldmann
    Metabolism Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA
    Nat Rev Immunol 6:595-601. 2006
    ..As discussed in this Review, the biology of these cytokines will affect the development of novel therapies for malignancy and autoimmune diseases, as well as the design of vaccines against infectious diseases...
  70. doi request reprint Antibody-based therapy of leukaemia
    John C Morris
    Metabolism Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892 1457, USA
    Expert Rev Mol Med 11:e29. 2009
    ..The antibodies can also be armed with cellular toxins or radionuclides to enhance the destruction of leukaemia cells...
  71. pmc IL-15 enhances the in vivo antitumor activity of tumor-reactive CD8+ T cells
    Christopher A Klebanoff
    Howard Hughes Medical Institute National Institutes of Health Research Scholars Program, Bethesda, MD 20814, USA
    Proc Natl Acad Sci U S A 101:1969-74. 2004
    ..These results provide several avenues for improving adoptive immunotherapy of cancer in patients...
  72. pmc Development of smallpox vaccine candidates with integrated interleukin-15 that demonstrate superior immunogenicity, efficacy, and safety in mice
    Liyanage P Perera
    Metabolism Branch, Center for Cancer Research, National Cancer Institute, Bldg 10, Bethesda, MD 20892 1374, USA
    J Virol 81:8774-83. 2007
    ..Thus, Wyeth IL-15 and MVA IL-15 viruses hold promise as more-efficacious and safe alternatives to the Dryvax vaccine...
  73. ncbi request reprint Proteasome inhibitor PS-341, a potential therapeutic agent for adult T-cell leukemia
    Chalet Tan
    Metabolism Branch, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland 20892 1374, USA
    Cancer Res 62:1083-6. 2002
    ....
  74. ncbi request reprint Modifications in synthesis strategy improve the yield and efficacy of geldanamycin-herceptin immunoconjugates
    Raya Mandler
    Metabolism Branch, National Cancer Institute, NIH, Bethesda, Maryland 20982 1002, USA
    Bioconjug Chem 13:786-91. 2002
    ..However, unlike H:ABA-GA, the immunoconjugate H:APA-GA caused stable tumor regression (in 25% of the recipients), showing a qualitative improvement with potential clinical relevance...
  75. ncbi request reprint Effective cancer therapy through immunomodulation
    Thomas A Waldmann
    National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892 1374, USA
    Annu Rev Med 57:65-81. 2006
    ....
  76. pmc MTS dye based colorimetric CTLL-2 cell proliferation assay for product release and stability monitoring of interleukin-15: assay qualification, standardization and statistical analysis
    Gopalan Soman
    Department of Process Analytics, Biopharmaceutical Development Program, SAIC Frederick, Inc, United States
    J Immunol Methods 348:83-94. 2009
    ..Applications of the assay were established including process development support, release of the rHuIL-15 product for pre-clinical and clinical studies, and for monitoring storage stability...
  77. ncbi request reprint The IL-2/IL-15 receptor systems: targets for immunotherapy
    Thomas A Waldmann
    Metabolism Branch, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland 20892 1374, USA
    J Clin Immunol 22:51-6. 2002
    ..Therapies directed toward inhibiting the actions of the inflammatory cytokine, IL-15, are proposed for an array of autoimmune disorders as well as diseases associated with the retrovirus human T-cell lymphotrophic virus 1...
  78. ncbi request reprint The meandering 45-year odyssey of a clinical immunologist
    Thomas A Waldmann
    Metabolism Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, 10 Center Drive, MSC 1374, Building 10, Room 4N115, Bethesda, Maryland 20892 1374, USA
    Annu Rev Immunol 21:1-27. 2003
    ..New forms of therapy directed at IL-2 and IL-15 receptors may be effective against certain neoplastic diseases and autoimmune disorders and in the prevention of allograft rejection...
  79. ncbi request reprint Micro-magnetic resonance lymphangiography in mice using a novel dendrimer-based magnetic resonance imaging contrast agent
    Hisataka Kobayashi
    Metabolism Branch, Center for Cancer Research, National Cancer, NIH, Bethesda, Maryland 20892, USA
    Cancer Res 63:271-6. 2003
    ....
  80. ncbi request reprint Improved renal clearance and tumor targeting of 99mTc-labeled anti-Tac monoclonal antibody Fab by chemical modifications
    Meyoung Kon Kim
    Department of Nuclear Medicine, Warren G Magnuson Clinical Center, Bethesda, Maryland 20892, USA
    Nucl Med Biol 29:139-46. 2002
    ..3% ID/g for 99mTc-MAG3-Fab, whereas the glycolation resulted in a drastic reduction of the renal uptake at 15 min. We demonstrated that the renal clearance and the tumor targeting of Fab could be optimized by chemical modifications...
  81. ncbi request reprint Activated clearance of a biotinylated macromolecular MRI contrast agent from the blood pool using an avidin chase
    Hisataka Kobayashi
    Metabolism Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA
    Bioconjug Chem 14:1044-7. 2003
    ..Moreover, it permits the repeated injection of the contrast agent and the "avidin switch" during a single MR experiment...
  82. ncbi request reprint Elevated serum-soluble interleukin-2 receptor levels in patients with anaplastic large cell lymphoma
    John E Janik
    Metabolism Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA
    Blood 104:3355-7. 2004
    ..Serum sIL-2R levels were elevated in both patients with recurrent disease...
  83. ncbi request reprint IL-15Ralpha recycles and presents IL-15 In trans to neighboring cells
    Sigrid Dubois
    Metabolism Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA
    Immunity 17:537-47. 2002
    ..Finally, these complexes on activated monocytes present IL-15 in trans to target cells such as CD8(+) T cells that express only IL-2/15Rbeta and gammac upon cell-cell interaction...
  84. doi request reprint Nanometer-scale organization of the alpha subunits of the receptors for IL2 and IL15 in human T lymphoma cells
    Bärbel I de Bakker
    Applied Optics Group, Faculty of Science and Technology, MESA Research Institute for Nanotechnology, University of Twente, PO Box 217, 7500 AE Enschede, The Netherlands
    J Cell Sci 121:627-33. 2008
    ..Our results should aid understanding the action of the IL2R-IL15R system in T cell function and also might contribute to the more rationale design of IL2R- or IL15R-targeted immunotherapy agents for treating human leukemia...
  85. ncbi request reprint GPI-microdomains (membrane rafts) and signaling of the multi-chain interleukin-2 receptor in human lymphoma/leukemia T cell lines
    Janos Matko
    Department of Biophysics and Cell Biology, Cell Biophysics Research Group of the Hungarian Academy of Sciences, University of Debrecen, Health Science Center, Debrecen, Hungary
    Eur J Biochem 269:1199-208. 2002
    ..g. CD48). Based on these data, the integrity of these GPI-microdomains seems critical in signal transduction through the IL-2R complex...
  86. pmc Effective treatment of established human breast tumor xenografts in immunodeficient mice with a single dose of the alpha-emitting radioisotope astatine-211 conjugated to anti-HER2/neu diabodies
    Matthew K Robinson
    Department of Medical Oncology, Fox Chase Cancer Center, Philadelphia, Pennsylvania 19111, USA
    Clin Cancer Res 14:875-82. 2008
    ..We hypothesized that the C6.5 diabody, a noncovalent anti-HER2 single-chain Fv dimer, would be an ideal radioisotope carrier for the radioimmunotherapy of established tumors using the short-lived alpha-emitting radioisotope (211)At...
  87. pmc IL-2 and IL-15 receptor alpha-subunits are coexpressed in a supramolecular receptor cluster in lipid rafts of T cells
    György Vámosi
    Cell Biophysics Research Group of the Hungarian Academy of Sciences, Debrecen, Hungary
    Proc Natl Acad Sci U S A 101:11082-7. 2004
    ..In addition, both alpha-chains were at least partially homodimerized/oligomerized, which could be the basis of distinct signaling pathways by the two cytokines...
  88. ncbi request reprint Pretargeting radioimmunotherapy of a murine model of adult T-cell leukemia with the alpha-emitting radionuclide, bismuth 213
    Meili Zhang
    Metabolism Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA
    Blood 100:208-16. 2002
    ..The findings of this study support the use of this combination approach in a clinical trial in patients with IL-2R alpha-expressing leukemias...
  89. ncbi request reprint Detection of receptor trimers on the cell surface by flow cytometric fluorescence energy homotransfer measurements
    Laszlo Bene
    Department of Biophysics and Cell Biology, Medical and Health Science Center, Research Center for Molecular Medicine, University of Debrecen, Hungary
    Biochim Biophys Acta 1744:176-98. 2005
    ....
  90. ncbi request reprint Coimmunization with an optimized IL-15 plasmid results in enhanced function and longevity of CD8 T cells that are partially independent of CD4 T cell help
    Michele A Kutzler
    Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA
    J Immunol 175:112-23. 2005
    ..These data suggest a role for enhanced plasmid IL-15 as a candidate adjuvant for vaccine or immunotherapeutic studies...
  91. ncbi request reprint Interleukin-2 receptor-directed therapies for cutaneous lymphomas
    Francine M Foss
    Tufts New England Medical Center, 750 Washington Street, Boston, MA 02111, USA
    Hematol Oncol Clin North Am 17:1449-58. 2003
    ....