M.D./M.S, University of Nebraska, Immunology, 1986.
Major projects include: (1) development of tumor antigen specific vaccines for the prevention of solid tumor relapse, (2) generation and characterization of cytotoxic CD8+ and CD4+ helper T cells specific for tumor antigens for eventual use in adoptive immunotherapy to treat advanced stage disease, (3) evaluation of antibody responses to various cancer causing proteins for use as a potential cancer diagnostic, (4) development of biologically relevant animal models for solid tumors to assess the effect of the generation of an immune response to immunogenic cancer proteins and to evaluate different vaccine and adoptive immunotherapy strategies, (5) phase I/II clinical trials of peptide and DNA vaccines targeting specific cancer antigens, (6) phase I/II clinical trials of infusion of antigen competent T cells in patients with advanced stage solid tumors, (7) antigen discovery in solid tumors using molecular immunology and protein based techniques, and (8) development of in vivo imaging techniques for tracking tumor specific T cells and assessing the response to tumor specific immunotherapy.
Studies from our laboratory have demonstrated that some patients with breast cancer have existent immunity to the HER-2/neu (H2N) protein which is the product of the amplified HER-2/neu oncogene. Therefore, the H2N protein is a tumor antigen. Developing immunotherapy targeting the H2N oncogenic protein via therapeutic vaccination and infusion of H2N specific T cells is a major goal of our work. We have identified breast cancer patients with both specific antibody and specific T cell responses to the protein. In addition, we have been able to generate cytotoxic T cells (CD8+) with an ability to specifically kill breast cancer cells via recognition of H2N protein. The detection of immunity to an oncogenic protein intimately involved in the growth and malignant potential of breast cancer has several profound ramifications. Methods to augment the existent immunity such as T cell therapy or vaccination might have a therapeutic effect. Our laboratory is currently evaluating the potential use ofH2N immunity inthe treatment of breast cancer, and is identifying potential target epitopes for T cell and vaccine therapy.
In addition to human studies, we have developed an animal model to study the effect of generating immunity to the H2N protein. One important feature of the H2N oncoprotein is that it is a non-mutated , overexpressed normal protein. The rat is an ideal model. Rat neu is 89% homologous to human H2N and the distribution of normal neu is similar, being found at low levels inskin and digestive tract epithelium. The major issues we are addressing in the rat model are how best to circumvent tolerance to H2N and whether levels of immunity necessary for tumor eradication cause any autoimmune toxicity. These studies should bedirectly applicable to humans as the structure, function, expression, and distribution of H2N is homologous in rats and humans. Results from these investigations will be directly applicable to the
treatment of breast cancer patients.
Extrapolatingfrom animal models of T cell therapy, treatment of human breast cancer should be possible provided that enough immune T cells can be generated and provided that the T cells are immune to the appropriate antigen. Theoretically, H2N is an appropriatetarget antigen. It is our hope that T cellvaccines an T cell therapy will be of benefit in cancer therapy, and, in addition, give the patient the ability to
protect against future relapse by the augmentation of her own immune defenses.
HER - 2/neu
Alpha Omega Alpha
American Association for Cancer Research
American Association of Immunologists
American Society for Clinical Oncology
American Society of Hematology
Society of Biologic Therapy
Southwest Oncology Group
Women in Cancer Research
Honors and Awards
2007, Scholarship, American Association of Medical Schools Women's Facutly Seminar
2006-2008, Deputy Editor, Translational Oncology, Journal Clinical Oncology
2006, Science Forum Lecturer, University of Washington, College of Arts & Sciences
2006, Elected, Board of Directors, International Society of Biologic Therapy
2006, Award for Scientific Excellence, Cancer Treatment Research Foundation
2004, Elected, American Society of Clinical Investigation
2004-2006, Chair, Clinical Oncology Study Section (CONC), NIH/NCI
2003, Center of Women's Health Award for Outstanding Mentorship, University of Washington School of Medicine
2003, Celebrating Hope Award of Scientific Achievement, Olympic Medical Center Foundation
2001, Science in Medicine Lectureship, University of Washington College of Medicine
2000-2001, Mid-Career Investigator Award in Patient Oriented Research, National Cancer Institute
1995-2000, Clinical Investigator Award, National Cancer Institute
1995-2000, FIRST Award, National Cancer Institute
1995-2000, Clinical Investigator Award, Nathional Cancer Institute
1995, Science in Medicine, New Investigator Lectureship, University of Washington College of Medicine
1994-1996, ACS Physician Research Training Award,
1993-1995, Berlex Oncology Foundation Clinical Research Fellow,
1991, Upjohn Outstanding Oncology Fellow Award, University of Washington
1990-1991, Clinical Oncology Fellowship, American Cancer Society
1989, Alpha Omega Alpha,
2001-2006, Associate Member, Fred Hutchinson Cancer Research Center, Clinical Division
1999-2006, Associate Professor, University of Washington, Division of Oncology
1998-2004, Director, University of Washington, Tumor Vaccine Group
1994-1999, Assistant Professor, University of Washington, Division of Oncology
1993-1994, Acting Instructor, University of Washington, Division of Oncology
1989-1990, Instructor, University of Illinois, Department of Medicine
Surface Receptor Antigen Vaccines, Patent Number: Application #60/109106, , , .
T cell therapy directed against the HER-2/neu protein, Patent Number: 5876712, , , .
Methods for eliciting or enhancing reactivity to HER-2/neu protein, Patent Number: 5869445, , , .
Methods and compositions to generate immunity in humans against self-tumor antigens by immunization with homologous foreign proteins, Patent Number: 5846538, , , .
Immune reactivity to HER-2/neu protein for diagnosis, Patent Number: 5726023, , , .
Theraputic Delivery Using Compounds Self-Assembled into High Axial Ratio Microstructures, Patent Number: 6180114, , , .
Compounds for eliciting or enhancing immune reactivity to the HER-2/neu protein for prevention or treatment of malignancies in which the HER-2/neu oncogene is associated, Patent Number: 6075122, , , .
Immune reactivity to HER-2/neu protein for diagnosis and treatment of malignancies in which the Her-2/neu oncogene is associated, Patent Number: 5801005, , , .
Toxicities of Immunotherapy for the Practitioner.. Journal of clinical oncology : official journal of the American Society of Clinical Oncology.. 2015.
The Antigenic Repertoire of Premalignant and High-Risk Lesions.. Cancer prevention research (Philadelphia, Pa.). 8(4):266-270.. 2015.
Designing vaccines to prevent breast cancer recurrence or invasive disease.. Immunotherapy. 7(2):69-72.. 2015.
Preamble to the 2015 SITC immunotherapy biomarkers taskforce.. Journal for immunotherapy of cancer. 3:8.. 2015.
Mechanism of action of immunotherapy.. Seminars in oncology. 41 Suppl 5:S3-13.. 2014.
Th1 epitope selection for clinically effective cancer vaccines.. Oncoimmunology. 3(9):e954971.. 2014.
Elimination of IL-10-Inducing T-Helper Epitopes from an IGFBP-2 Vaccine Ensures Potent Antitumor Activity.. Cancer research. 74(10):2710-8.. 2014.
CCL21 and IFNγ Recruit and Activate Tumor Specific T cells in 3D Scaffold Model of Breast Cancer.. Anti-cancer agents in medicinal chemistry. 14(2):204-10.. 2014.
Natural history of tumor growth and immune modulation in common spontaneous murine mammary tumor models.. Breast cancer research and treatment. 148(3):501-10.. 2014.
Mining the pre-diagnostic antibody repertoire of TgMMTV-neu mice to identify autoantibodies useful for the early detection of human breast cancer.. Journal of translational medicine. 12(1):121.. 2014.
Evaluation of Cancer Immunity in Mice.. Cold Spring Harbor protocols.. 2013.
HER-2/neu vaccine-primed autologous T-cell infusions for the treatment of advanced stage HER-2/neu expressing cancers.. Cancer immunology, immunotherapy : CII.. 2013.
Expanding Assessments of Translational Research Programs: Supplementing Metrics With Value Judgments.. Evaluation & the health professions.. 2013.
Gamma delta T cells are activated by polysaccharide K (PSK) and contribute to the anti-tumor effect of PSK.. Cancer immunology, immunotherapy : CII.. 2013.
Therapeutic vaccines for ovarian cancer.. Gynecologic oncology.. 2013.
Proteomic profiling of the autoimmune response to breast cancer antigens uncovers a suppressive effect of hormone therapy.. Proteomics. Clinical applications. 7(5-6):327-336.. 2013.
Identification of putative immunologic targets for colon cancer prevention based on conserved gene upregulation from preinvasive to malignant lesions.. Cancer prevention research (Philadelphia, Pa.). 6(7):666-74.. 2013.
Can immunity to breast cancer eliminate residual micrometastases? Clinical cancer research : an official journal of the American Association for Cancer Research. 19(23):6398-403.. 2013.
A Multiantigen Vaccine Targeting Neu, IGFBP-2, and IGF-IR Prevents Tumor Progression in Mice with Preinvasive Breast Disease.. Cancer prevention research (Philadelphia, Pa.). 6(12):1273-82.. 2013.
The invisible arm of immunity in common cancer chemoprevention agents.. Cancer prevention research (Philadelphia, Pa.). 6(8):764-73.. 2013.
Evaluation of Known Oncoantibodies, HER2, p53, and Cyclin B1, in Prediagnostic Breast Cancer Sera.. Cancer prevention research (Philadelphia, Pa.).. 2012.
Transcriptome-wide studies of merkel cell carcinoma and validation of intratumoral CD8+ lymphocyte invasion as an independent predictor of survival.. Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 29(12):1539-46.. 2011.