Tumor Specific Immunotherapy of Mammary Cancer.
Annual rept. 17 Aug 94-16 Aug 95,
MARYLAND UNIV BALTIMORE COUNTY CATONSVILLE
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For many patients with mammary cancer the primary tumor can be successfully treated by surgical removal, however the long-term prognosis is not favorable because of the high frequency of metastatic disease which is not treatable by current approaches. Our goal is to develop vaccination strategies to minimize metastatic disease. We postulate that an improvement in the generation of mammary carcinoma-specific CD4 T helper lymphocytes will facilitate development of CD8-mediated tumor immunity. To enhance the activation of CD4 T helper cells, autologous mouse mammary tumor cells are being transfected with syngeneic MHC class II genes plus a variety of costimulatory I and adhesion molecules, including B7-1, B7-2, 4-1 BB ligand, and ICAM-1. The genetically modified tumor cells should be able to directly present mammary tumor peptides to CD4 T cells, thereby facilitating their activation. Transfectants are being tested for their tumorigenicity, for their ability to protect tumor-free mice from subsequent exposure to mammary tumor cells, and for their ability to vaccinate against spontaneous metastatic disease in a post-surgical situation.
- Medicine and Medical Research
- Anatomy and Physiology