Nora Disis

Appointments and Affiliations

 
 
University of Washington
School of Medicine
Medicine
Oncology
Professor, Appointed: 2006
University of Washington
Translational Science
Associate Dean, Appointed: 2007
University of Washington
Institute for Translational Health Sciences
Director, Appointed: 2007
Fred Hutchinson Cancer Research Center
Clinical Research Division
Member, Appointed: 2006
University of Washington
General Clincial Research Center
Director, Appointed: 2004
University of Washington
School of Medicine
Center for Translational Medicine in Women's Health
Director, Appointed: 2004
Professional Headshot of Mary L. (Nora) Disis

Mailing Address

815 Mercer Street
2nd Floor
Tumor Vaccine Group
Box 358050
Seattle, Washington 98109-8050
United States

Contact

Phone: (206) 616-1823
Fax: (206) 685-3128
ndisis@u.washington.edu

Degrees

M.D./M.S, University of Nebraska, Immunology, 1986.

Research Interests

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.

Cancer Vaccines
Tumor Immunology
Immunotherapy
T-Cell Therapy
Immunodiagnostics
HER - 2/neu
Antigen Discovery

Additional Experience

Breast Cancer
Ovarian Cancer
 

Memberships

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,

Previous Positions

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

Patents

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, , , .

Funding

  • NCI: Mechanisms of Immunomodulatory and Anti-Tumor Actions of Polysaccharide Krestin, $250,000, 2007 to 2011.
  • NIH: Institute of Translational Health Sciences, $6,513,229, 2007 to 2012.
  • NCI: Developing a Serum Antibody-Based Assay for the Diagnosis of Colorectal Cancer, $30,000, 2007 to 2008.
  • Komen Foundation: Immunologic Signature in Early Stage Breast Cancer, $100,000, 2007 to 2011.
  • Department of Defense: Identification of Tumor Rejection Antigens Using a Mouse Tumor Rejection Model, $100,000, 2006 to 2009.
  • Arnold and Mabel Beckman Foundation: Phase I/II Study of Combination Immunotherapy in Advanced Stage Breast Cancer, $125,000, 2006 to 2008.
  • Ovarian Cancer Research Fund: Cooperative Ovarian Cancer Group for Immunotherapy, $107,811, 2005 to 2008.
  • Department of Defense: Phase II Study of HER-2/neu Intracellular Domain Peptide-Based Vaccine Administered to Stage IV HER2 Positive Breast Cancer Patients Receiving Trastuzumab, $300,000, 2004 to 2009.
  • NCI: Pacific Ovarian Cancer Research Consortium: Leadership Core, $151,964, 2004 to 2009.
  • NCI: Multi-antigen Vaccines for Breast Cancer Prevention, $225,000, 2003 to 2008.
  • NCI: Phase I Clinical Trial of a HER2 ICD Plasmid Based DNA Vaccine in Patients with HER2 Overexpressing Breast and Ovarian Cancer, $904,715, 2003 to 2008.

Recent Publications

2014
2013
Disis, ML, Stanton SE.  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. Abstract
2012
2011
2009
2008
Cheever, MA, Schlom J, Weiner LM, Lyerly KH, Disis ML, Greenwood A, Grad O, Nelson WG.  2008.  Translational Research Working Group developmental pathway for immune response modifiers.. Clinical cancer research : an official journal of the American Association for Cancer Research. 14(18):5692-9. Abstract