Tumor-Specific Immunotherapy of Mammary Cancer
Abstract
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 lymphocytes will facilitate development of CD8+ T cell mediated immunity. We have generated vaccines consisting of mouse mammary tumor cells transfected with MHC class II, costimulatory (B7. 1 or CD8O), and superantigen (SEB) genes, and have shown that the vaccines directly present tumor encoded antigens to CD4+ T cells.. To test vaccine efficacy, we have developed a mouse mammary carcinoma model that closely parallels human breast cancer. The BALBic-derived 4T1 tumor spontaneously metastasizes throughout the body following inoculation into the mammary gland. Metastases are well established within 2-3 weeks of inoculation, and removal of primary tumor does not alter metastatic disease progression. Treatment with the vaccines significantly decreases the number of metastatic cells and increases survival time following surgical removal of primary tumor. Therapy with the class II/CD8O vaccine plus 1L-12 also reduces metastatic disease, and probably involves chemokines in addition to T lymphocytes.
Document Details
- Document Type
- Technical Report
- Publication Date
- Apr 01, 2000
- Accession Number
- ADA387654
Entities
People
- Suzanne Ostrand-Rosenberg
Organizations
- University of Maryland, Baltimore County