Affiliation: Mayo Clinic
- Improved Survival of HER2+ Breast Cancer Patients Treated with Trastuzumab and Chemotherapy Is Associated with Host Antibody Immunity against the HER2 Intracellular DomainKeith L Knutson
Department of Immunology, Mayo Clinic, Jacksonville, Florida
Cancer Res 76:3702-10. 2016..6, P < 0.0001) and OS (HR = 1.4, P = 0.0006). Overall, the findings further demonstrate the importance of the adaptive immune system in the efficacy of trastuzumab-containing regimens. Cancer Res; 76(13); 3702-10. ©2016 AACR. ..
- Regulatory T cells, inherited variation, and clinical outcome in epithelial ovarian cancerKeith L Knutson
Cancer Vaccines and Immune Therapies Program, The Vaccine and Gene Therapy Institute of Florida, Port St Lucie, FL, USA
Cancer Immunol Immunother 64:1495-504. 2015....
- Functional folate receptor alpha is elevated in the blood of ovarian cancer patientsEati Basal
Department of Immunology, Mayo Clinic, Rochester, MN, USA
PLoS ONE 4:e6292. 2009..In the current study, the goal was to determine whether ovarian cancer patients (n = 30) had elevated serum levels of a fully functional intact FRalpha compared to matched healthy controls (n = 30)...
- Optimizing patient derived mesenchymal stem cells as virus carriers for a phase I clinical trial in ovarian cancerEmily K Mader
Department of Molecular Medicine, Mayo Clinic, Rochester, MN 55905, USA
J Transl Med 11:20. 2013..In preparation for a clinical trial to use MSC as MV carriers, we obtained cells from ovarian cancer patients and evaluated feasibility and safety of this approach...
- A profile of immune response to herpesvirus is associated with radiographic joint damage in rheumatoid arthritisJohn M Davis
Division of Rheumatology, Department of Medicine, College of Medicine, Mayo Clinic 200 First Street SW, Rochester, MN 55905, USA
Arthritis Res Ther 14:R24. 2012..This study was undertaken to identify profiles of immune response that correlate with radiographic joint damage as a first step toward the discovery of new pathogenic mechanisms of joint destruction in RA...
- Vaccination with a plasmid DNA encoding HER-2/neu together with low doses of GM-CSF and IL-2 in patients with metastatic breast carcinoma: a pilot clinical trialHåkan Norell
Department of Oncology and Pathology, Cancer Center Karolinska, Karolinska Institutet, Stockholm, Sweden
J Transl Med 8:53. 2010..Here we report the first administration of a Her2-plasmid DNA (pDNA) vaccine in humans...
- Polymorphisms in NF-kappaB inhibitors and risk of epithelial ovarian cancerKristin L White
Mayo Clinic College of Medicine, Rochester, MN, USA
BMC Cancer 9:170. 2009..Inhibitors of kappaB (IkappaB) prevent NF-kappaB activation by sequestering NF-kappaB proteins in the cytoplasm until IkappaB proteins are phosphorylated and degraded...
- T-cell immunity to the folate receptor alpha is prevalent in women with breast or ovarian cancerKeith L Knutson
Department of Immunology, Mayo Clinic College of Medicine, Rochester, MN 55905, USA
J Clin Oncol 24:4254-61. 2006..A candidate antigen is the folate receptor alpha (FRalpha), which is overexpressed in breast and ovarian cancers. Our goal in this study was to attain a better understanding of the extent of endogenous FRalpha immunity...
- CD4 regulatory T cells in human cancer pathogenesisKeith L Knutson
Department of Immunology, Mayo Clinic College of Medicine, Mayo Clinic, 342C Guggenheim, 200 First Street SW, Rochester, MN 55905, USA
Cancer Immunol Immunother 56:271-85. 2007..e., autoimmune disease). In this review, the biology of human CD4(+) Tregs is discussed along with their involvement in malignancies and emerging strategies to block their function...
- Tumor antigen-specific T helper cells in cancer immunity and immunotherapyK L Knutson
Department of Immunology, Mayo Clinic College of Medicine, 342C Guggenheim Bldg, 200 First St SW, Rochester, MN 55906, USA
Cancer Immunol Immunother 54:721-8. 2005....
- Laboratory analysis of T-cell immunityKeith L Knutson
Department of Immunology, Mayo Clinic College of Medicine, Rochester, MN 55905, USA
Front Biosci 11:1932-44. 2006..Informative immunologic monitoring of T cells will be one of the driving forces in advancing the field of tumor immunology...
- Augmenting T helper cell immunity in cancerK L Knutson
Department of Immunology, Mayo Clinic College of Medicine, 200 First St SW, Rochester, MN 55906, USA
Curr Drug Targets Immune Endocr Metabol Disord 5:365-71. 2005..Over the next decade, studies should begin to further define how we can manipulate the Th immune effector arm to achieve effective antitumor immunity...
- Strong-arming immune regulation: suppressing regulatory T-cell function to treat cancersKeith L Knutson
Department of Immunology, Mayo Clinic College of Medicine, 342C Guggenheim, 200 First St SW, Mayo Clinic, Rochester, MN 55905, USA
Future Oncol 2:379-89. 2006..e., autoimmune disease). In this review, the biology of Tregs is discussed along with their involvement in malignancies and emerging strategies to block their function...
- IL-2 immunotoxin therapy modulates tumor-associated regulatory T cells and leads to lasting immune-mediated rejection of breast cancers in neu-transgenic miceKeith L Knutson
Department of Immunology, Mayo Clinic College of Medicine, 342C Guggenheim, 200 First Street SW, Rochester, MN 55905, USA
J Immunol 177:84-91. 2006....
- Immunoediting of cancers may lead to epithelial to mesenchymal transitionKeith L Knutson
Department of Immunology, Mayo Clinic, Rochester, MN 55905, USA
J Immunol 177:1526-33. 2006..Understanding the mechanisms by which tumors are immunoedited will likely lead to a better understanding of how tumors evade immune detection...
- Immune-induced epithelial to mesenchymal transition in vivo generates breast cancer stem cellsMarta Santisteban
Department of Oncology, Mayo Clinic, Rochester, Minnesota 55905, USA
Cancer Res 69:2887-95. 2009..These findings have several important implications related to disease progression and relapse...
- An HLA-DR-degenerate epitope pool detects insulin-like growth factor binding protein 2-specific immunity in patients with cancerKimberly R Kalli
Departments of Oncology, Immunology, and Health Sciences Research, Mayo Clinic, Rochester, Minnesota, USA
Cancer Res 68:4893-901. 2008..All four peptides are naturally processed and presented to CD4 T-cells. The degenerate pool of peptides covers nearly 80% of patients and may be useful for augmenting CD4 T-cell immunity in patients undergoing immunization...
- Peptide vaccine given with a Toll-like receptor agonist is effective for the treatment and prevention of spontaneous breast tumorsPilar Nava-Parada
Department of Immunology, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA
Cancer Res 67:1326-34. 2007..e., epitope spreading). These results suggest that similar strategies should be followed for conducting clinical studies in patients...
- Intraepithelial effector (CD3+)/regulatory (FoxP3+) T-cell ratio predicts a clinical outcome of human colon carcinomaFrank A Sinicrope
Miles and Shirley Fiterman Digestive Disease Center, Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota 55905, USA
Gastroenterology 137:1270-9. 2009..We investigated whether the intratumoral densities of FoxP3(+) and effector CD3(+) lymphocytes are associated with prognosis of patients with colon cancer...
- A degenerate HLA-DR epitope pool of HER-2/neu reveals a novel in vivo immunodominant epitope, HER-2/neu88-102Lavakumar Karyampudi
Department of Immunology, Mayo Clinic, Rochester, Minnesota, USA
Clin Cancer Res 16:825-34. 2010..Our goal in this study was to identify broad coverage HLA-DR epitopes of HER-2/neu, an antigen that is highly expressed in a variety of carcinomas...
- Immune promotion of epithelial-mesenchymal transition and generation of breast cancer stem cellsJennifer M Reiman
Department of Immunology, Mayo Clinic, Rochester, Minnesota, USA
Cancer Res 70:3005-8. 2010..These studies provide a window to understanding how BCSC arise and are maintained within tumors, and how to best target these processes for therapeutic benefit...
- Analysis of complex biomarkers for human immune-mediated disorders based on cytokine responsiveness of peripheral blood cellsJohn M Davis
Division of Rheumatology, Department of Medicine, College of Medicine, Mayo Clinic, Rochester, MN 55905, USA
J Immunol 184:7297-304. 2010..Thus, our approach lays the foundation for the development of immunologic "signatures" that could be useful in predicting disease course and monitoring the outcomes of therapy among patients with immune-mediated diseases...
- Casp8p41 expression in primary T cells induces a proinflammatory responseJulie A Taylor
Division of Infectious Diseases, Rochester, Minnesota, USA
AIDS 24:1251-8. 2010..Herein, we questioned whether Casp8p41-induced NFkappaB activation impacts the cytokine profile of cells expressing Casp8p41...
- Folate receptor alpha as a tumor target in epithelial ovarian cancerKimberly R Kalli
Division of Medical Oncology, Mayo Clinic College of Medicine, Rochester, MN 55905, USA
Gynecol Oncol 108:619-26. 2008..The goal of this study is to improve historical data that lack specific information about FRalpha expression in rare histological subtypes, primary disease versus metastatic foci, and recurrent disease...
- Identification of a broad coverage HLA-DR degenerate epitope pool derived from carcinoembryonic antigenLavakumar Karyampudi
Department of Immunology, College of Medicine, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA
Cancer Immunol Immunother 59:161-71. 2010..Patients with breast or ovarian cancer demonstrate pre-existent immune responses to the tumor antigen CEA. The degenerate pool of CEA peptides may be useful for augmenting CD4 T cell immunity...
- Beneficial effect of TRAIL on HIV burden, without detectable immune consequencesBrett D Shepard
Mayo Clinic, Rochester, Minnesota, USA
PLoS ONE 3:e3096. 2008....
- The endogenous danger signal, crystalline uric acid, signals for enhanced antibody immunityMarshall D Behrens
Department of Immunology, Mayo Clinic College of Medicine, Mayo Clinic, Rochester, MN 55905, USA
Blood 111:1472-9. 2008..Understanding the nature of endogenous danger signals released from dying cells may aid in a better understanding of mechanisms of immune recognition of self...
- Adoptive T cell therapy of solid cancersKeith L Knutson
Mayo Clinic College of Medicine, 342D Guggenheim, 200 First St SW, Mayo Clinic, Rochester, MN 55905, USA
Cancer Immunol Immunother 55:96-103. 2006..Some of the major problems are sources of tumor-specific T cells, ex vivo expansion, persistence, and anti-tumor activity. This review overviews the nature of these problems and some of the emerging solutions...
- Tumor-infiltrating Foxp3-CD4+CD25+ T cells predict poor survival in renal cell carcinomaSameer A Siddiqui
Department of Urology, Mayo Clinic, Rochester, Minnesota 55905, USA
Clin Cancer Res 13:2075-81. 2007..We tested for the presence of putative Tregs within renal cell carcinoma (RCC) tumors...
- Tumor immunoediting and immunosculpting pathways to cancer progressionJennifer M Reiman
Department of Immunology, Mayo Clinic College of Medicine, 200 First Street SW, Rochester, MN 55905, United States
Semin Cancer Biol 17:275-87. 2007..Regardless, these immune-induced alterations could contribute to cancer pathogenesis. Understanding the mechanisms by which tumors evade immunity will be important for disease prevention and therapeutics...
- Induction of a Th1 response from Th2-polarized T cells by activated dendritic cells: dependence on TCR:peptide-MHC interaction, ICAM-1, IL-12, and IFN-gammaSuresh Radhakrishnan
Department of Immunology, Mayo Clinic College of Medicine, 200 First Street SW, Rochester, MN 55905, USA
J Immunol 178:3583-92. 2007..Because the regulation of mouse and human DC by B7-DC XAb overlaps in several significant ways, immune modulation with B7-DC XAb is a potential strategy for treating Th2-mediated diseases...
- Renal hemodynamic, inflammatory, and apoptotic responses to lipopolysaccharide in HO-1-/- miceMichal J Tracz
Division of Nephrology and Hypertension, Department of Pathology, Mayo Clinic College of Medicine, 200 First Street SW, Rochester, MN 55905, USA
Am J Pathol 170:1820-30. 2007..Because polymorphisms in the HO-1 gene with diminished HO activity predispose to human disease, we speculate that our findings may be relevant to the clinical outcome in patients with sepsis syndromes...
- Immunization of cancer patients with HER-2/neu-derived peptides demonstrating high-affinity binding to multiple class II allelesLupe G Salazar
Tumor Vaccine Group, Division of Oncology, University of Washington, Seattle, Washington, USA
Clin Cancer Res 9:5559-65. 2003..Furthermore, we questioned whether MHC binding affinity could predict the in vivo immunogenicity of the HER-2/neu helper peptides...
- Plasmid-based vaccines encoding rat neu and immune stimulatory molecules can elicit rat neu-specific immunityMary L Disis
Tumor Vaccine Group, Division of Oncology, University of Washington, Seattle, WA 98195 6527, USA
Mol Cancer Ther 2:995-1002. 2003..DNA vaccines encoding neu, when given in combination with both CD137L and either CD80 or CD86, can induce cellular and humoral immunity and result in an antitumor effect...
- Effect of dose on immune response in patients vaccinated with an her-2/neu intracellular domain protein--based vaccineMary L Disis
Tumor Vaccine Group, Oncology, University of Washington, Seattle, WA 98195 6527, USA
J Clin Oncol 22:1916-25. 2004..To evaluate the safety of an HER-2/neu intracellular domain (ICD) protein vaccine and to estimate whether vaccine dose impacts immunogenicity...
- Immunologic principles and immunotherapeutic approaches in ovarian cancerKeith L Knutson
Tumor Vaccine Group, 1959 Northeast Pacific Street, Box 356527, HSB BB1321, University of Washington, Seattle, WA 98195, USA
Hematol Oncol Clin North Am 17:1051-73. 2003..It is hoped that discoveries at the bench along with lessons learned in prior clinical trials soon will allow clinicians to develop rationally based immunologic strategies to treat and prevent ovarian cancer...
- Flt3 ligand as a vaccine adjuvant in association with HER-2/neu peptide-based vaccines in patients with HER-2/neu-overexpressing cancersMary L Disis
Division of Oncology, University of Washington, Seattle, WA 98195 6527, USA
Blood 99:2845-50. 2002..Finally, vaccine regimens including FL as a vaccine adjuvant were associated with the development of apparent autoimmune phenomena in some patients...
- Clonal diversity of the T-cell population responding to a dominant HLA-A2 epitope of HER-2/neu after active immunization in an ovarian cancer patientKeith L Knutson
Division of Oncology, Department of Medicine, University of Washington, Seattle, WA 98195 6527, USA
Hum Immunol 63:547-57. 2002..These results suggest that a tumor antigen TCR, directed against a specific epitope, can be markedly polyclonal at multiple levels including CD4/CD8 and TCR...
- Immunization of cancer patients with a HER-2/neu, HLA-A2 peptide, p369-377, results in short-lived peptide-specific immunityKeith L Knutson
Division of Oncology, University of Washington, Seattle 98195 6527, USA
Clin Cancer Res 8:1014-8. 2002..However, the magnitude of the responses were low, as well as short-lived, suggesting that CD4+ T-cell help is required for lasting immunity to this epitope...
- Soluble cytokines can act as effective adjuvants in plasmid DNA vaccines targeting self tumor antigensMary L Disis
Division of Oncology, University of Washington, Seattle, Washington 98195 6527, USA
Immunobiology 207:179-86. 2003..Antibodies directed against rat neu were not elicited with this approach, indicating that the neu specific T cell immune response elicited with plasmid DNA was skewed towards cell-mediated rather than humoral immunity...
- Generation of T-cell immunity to the HER-2/neu protein after active immunization with HER-2/neu peptide-based vaccinesMary L Disis
Division of Oncology and Department of Dermatology, University of Washington, Seattle 98195 6527, USA
J Clin Oncol 20:2624-32. 2002....
- Blockade of B7-H1 improves myeloid dendritic cell-mediated antitumor immunityTyler J Curiel
Tulane University Health Science Center, New Orleans, Louisiana, USA
Nat Med 9:562-7. 2003..Therefore, upregulation of B7-H1 on MDCs in the tumor microenvironment downregulates T-cell immunity. Blockade of B7-H1 represents one approach for cancer immunotherapy...
- Immunotherapy for breast cancerKeith L Knutson
Tumor Vaccine Group, University of Washington, Seattle, WA, USA
Cancer Chemother Biol Response Modif 20:351-69. 2002
- Neu antigen-negative variants can be generated after neu-specific antibody therapy in neu transgenic miceKeith L Knutson
University of Washington, Tumor Vaccine Group, Department of Oncology, Seattle, Washington, USA
Cancer Res 64:1146-51. 2004....
- Antitumor efficacy of CD137 ligation is maximized by the use of a CD137 single-chain Fv-expressing whole-cell tumor vaccine compared with CD137-specific monoclonal antibody infusionHongtao Zhang
Department of Pathology, Center for Translational Medicine in Women s Health, University of Washington, Seattle, USA
Mol Cancer Ther 5:149-55. 2006..In contrast, repeated administration of either of two different anti-CD137 monoclonal antibodies did not induce complete tumor regression, although tumor growth was delayed...
- Tumor cells transduced with the MHC class II Transactivator and CD80 activate tumor-specific CD4+ T cells whether or not they are silenced for invariant chainJames A Thompson
Department of Biological Sciences, University of Maryland Baltimore County, Baltimore, MD 21250, USA
Cancer Res 66:1147-54. 2006..Therefore, tumor cells transduced with the CIITA, CD80, and with or without Ii siRNA present endogenously synthesized tumor antigens and are potential vaccines for activating tumor-specific CD4+ T cells...
- Emergence of immune escape variant of mammary tumors that has distinct proteomic profile and a reduced ability to induce "danger signals"Masoud H Manjili
Department of Microbiology and Immunology, Virginia Commonwealth University, Massey Cancer Center, Richmond, VA, 23298, USA
Breast Cancer Res Treat 96:233-41. 2006..Based on these findings, we propose to target novel antigens over-expressed in the escape variant of breast tumors to treat primary tumor and to prevent tumor relapse...
- Humoral epitope-spreading following immunization with a HER-2/neu peptide based vaccine in cancer patientsMary L Disis
Tumor Vaccine Group, Division of Oncology, University of Washington, Seattle, Washington 98195 6527, USA
J Clin Immunol 24:571-8. 2004..Intermolecular epitope-spreading to p53 was evident in 20% of vaccinated patients. Of those patients who developed new immunity to p53, 71% had demonstrated antibody epitope-spreading within HER-2/neu...
- The tumor antigen repertoire identified in tumor-bearing neu transgenic mice predicts human tumor antigensHailing Lu
Tumor Vaccine Group, Center for Translational Medicine in Women s Health, University of Washington, Seattle, WA 98195, USA
Cancer Res 66:9754-61. 2006..Our results indicate that neu-tg mice bearing spontaneous tumors develop humoral immunity to their tumors similar to cancer patients and that tumor antigens identified in transgenic mouse may predict immunogenic human homologues...
- HER-2/neu vaccinesMary L Disis
University of Washington, Seattle 98195 6527, USA
Cancer Chemother Biol Response Modif 21:275-85. 2003
- HER-2/neu antigen loss and relapse of mammary carcinoma are actively induced by T cell-mediated anti-tumor immune responsesMaciej Kmieciak
Department of Microbiology and Immunology, VCU School of Medicine, Massey Cancer Center, Richmond, VA 23298, USA
Eur J Immunol 37:675-85. 2007..This appears to be due to methylation of the neu promoter. Together, these data suggest that neu antigen loss is an active process that occurs in primary tumors due to the neu-targeted anti-tumor immune responses...
- Tumor antigen-specific T-cell expansion is greatly facilitated by in vivo primingYushe Dang
Tumor Vaccine Group, Center for Translational Medicine in Women s Health, University of Washington, Seattle, WA 98109, USA
Clin Cancer Res 13:1883-91. 2007..In this study, we evaluated the feasibility of expanding HER-2/neu-specific T cells derived from peripheral blood ex vivo following in vivo priming with a HER-2/neu peptide vaccine...
- Specific recruitment of regulatory T cells in ovarian carcinoma fosters immune privilege and predicts reduced survivalTyler J Curiel
Tulane University Health Science Center, New Orleans, Louisiana 70112, USA
Nat Med 10:942-9. 2004..This specific recruitment of T(reg) cells represents a mechanism by which tumors may foster immune privilege. Thus, blocking T(reg) cell migration or function may help to defeat human cancer...
- Signatures associated with rejection or recurrence in HER-2/neu-positive mammary tumorsAndrea Worschech
Department of Microbiology and Immunology, Virginia Commonwealth University School of Medicine, Massey Cancer Center, Richmond, VA 23298, USA
Cancer Res 68:2436-46. 2008..These data provide a road map for the identification of novel biomarkers of immune responsiveness in clinical trials...
- Technology evaluation: DCVax, Northwest BiotherapeuticsKeith L Knutson
University of Washington, Tumor Vaccine Group, Seattle 98195, USA
Curr Opin Mol Ther 4:403-7. 2002..DCVax-Brain is currently undergoing phase II clinical trials, and DCVax-Lung recently received approval from the US FDA for phase I clinical trials...
- GMK (Progenics Pharmaceuticals)Keith L Knutson
University of Washington, Tumor Vaccine Group, Seattle, 98195, USA
Curr Opin Investig Drugs 3:159-64. 2002..In July 2001, Ladenburg Thalmann predicted a $257 million market potential for GMK in the US, with the non-US market equivalent to the US market. A launch date of 2005 in the US, with a worldwide launch in 2006, was estimated ...
- Augmented HER-2 specific immunity during treatment with trastuzumab and chemotherapyClare Taylor
Department of Microbiology, College of Physicians and Surgeons, Columbia University, New York, NY 10027 6902, USA
Clin Cancer Res 13:5133-43. 2007..We have assessed whether immune sensitization to the HER-2/neu tumor antigen occurs during treatment with the anti-HER-2/neu monoclonal antibody trastuzumab...
- Peptide-based vaccines in breast cancerMary L Disis
Tumor Vaccine Group, Oncology, University of Washington, Seattle, WA 98195 6527, USA
Breast Dis 20:3-11. 2004..Peptide based vaccines are one of the most commonly studied vaccine strategies targeting breast cancer...
- Adoptive T-cell therapy for the treatment of solid tumoursKeith L Knutson
Division of Oncology, University of Washington, 1959 NE Pacific Street, HSB BB1321, Box 356527, Seattle, WA 98195 6527, USA
Expert Opin Biol Ther 2:55-66. 2002..In addition, advanced imaging techniques, such as positron emission tomography (PET), are being implemented in order to better define the in vivo function of ex vivo expanded tumour-specific T-cells...
- Analysis of serum folate receptor and antibody level for ovarian cancer detectionKeith Knutson; Fiscal Year: 2007..unreadable] [unreadable] [unreadable]..
- Ex vivo expansion of HER-2/neu specific T helper cellsKeith Knutson; Fiscal Year: 2008..abstract_text> ..
- HLA classl complex expression in breast cancer immunityKeith Knutson; Fiscal Year: 2009..The results will likely lead to the identification of specific molecule associated with antigen presentation that could be either a novel therapeutic target or biomarker of disease outcome. ..