Ex Vivo Expansion of HER2-Specific T Cells for the Treatment of HER2-Overexpressing Breast Cancer
Abstract
The identification and characterization of tumor antigens has facilitated the development of immune-based cancer prophylaxis and therapy. Cancer vaccines, like viral vaccines, may be effective in cancer prevention. Adoptive T cell therapy, in contrast, may be more efficacious for the eradication of existing malignancies. I am examining the feasibility of antigen-specific adoptive T cell therapy for the treatment of established cancer in the HER- 2/neu model. Transgenic mice overexpressing rat neu in mammary tissue develop malignancy, histologically similar to human HER-2/neu breast cancer. These nice can be effectively immunized against a challenge with neu' tumor cells. Adoptive transfer of neu-specific T cells into tumor-bearing mice eradicates malignancy. Effective T cell therapy relies on optimization of the ex vivo expansion of antigen-specific T cells. Two important elements of ex vivo antigen-specific T cell growth that have been identified are (1) the pre-existing levels of antigen- specific T cells, and, (2) the cytokine milieu used during ex vivo expansion of the T cells. Phase I clinical trials of HER-2/neu-based peptide vaccination in human cancer patients have demonstrated that increased levels of HER-2/neu-specific T cells can be elicited after active immunization. Initiating cultures with greater numbers of antigen-specific T cell lines and clones facilitates expansion. In addition, cytokines, such as IL-l2, when added during ex vivo culturing along with IL-2 can selectively expand antigen-specific T cells IL-l2 also enhances antigen-specific functional measurements such as IFN-gamma and TNF-alpha release. Refinements in ex vivo expansion techniques may greatly improve the feasibility of tumor-antigen T cell-based therapy for the treatment of advanced stage HER-2/neu-overexpressing breast malignancy.
Document Details
- Document Type
- Technical Report
- Publication Date
- May 01, 2001
- Accession Number
- ADA392841
Entities
People
- Keith L Knutson
- Mary Disis
Organizations
- University of Washington