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Immunology |
Department of Biological Sciences, University of Maryland Baltimore County, Baltimore, Maryland 21250 [B. A. P., E. M., S. O-R.]; Enerjen, Carmel, California 93921 [D. S. T.]; and Department of Molecular Genetics and Biochemistry, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15261 [S. K.]
One of the leading causes of death for women is metastatic breast cancer. Because most animal tumors do not accurately model clinical metastatic disease, the development of effective therapies has progressed slowly. In this study, we establish the poorly immunogenic mouse 4T1 mammary carcinoma as a postsurgical animal model. 4T1 growth characteristics parallel highly invasive human metastatic mammary carcinoma and, at the time of surgery, the extent of disease is comparable with human stage IV breast cancer. Progress in understanding the immune response has led to innovative immune-based anticancer therapies. Here, we test in this postsurgical model, a novel cell-based vaccine, combining MHC class II, CD80 (B7.1), and SEB superantigen. Effective treatment of tumor-bearing mice with this immunotherapy requires expression of all three molecules. Mean survival time is extended from 5–7.5 weeks for control-treated mice to 6–10.5 weeks for therapy-treated mice. Increased survival is accompanied by a maximum of 100-fold decrease in clonogenic lung metastases. These therapeutic effects are particularly noteworthy because: (a) the postoperative model demonstrates that early metastases responsible for morbidity are established by 2 weeks after tumor inoculation with 7 x 103 parental 4T1 cells into the mammary gland; (b) the immunotherapy is started 4 weeks after tumor inoculation when the mice contain extensive, pre-established, disseminated metastases; and (c) CD4+ and CD8+ T cells are required for the effect.
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