Strategies for the Development of Vaccines to Treat Breast Cancer

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Abstract
Spontaneous regressions of human tumors have been reported in different types of cancer, especially in melanoma and renal cell carcinoma (Gromet et al. 1978; Balch et al. 1992), but also in other types of cancer such as non-small cell lung cancer, bladder carcinoma, and breast cancer. These observations suggest the interaction of the immune system with antigenic determinants presented by the tumor. Early attempts to activate the immune system against tumor growth were based on observations made in cultured melanoma cells which were shown to be lysed by autologous CD8+T lymphocytes in vitro. The clinical translation of this observation was applied to single patients with metastatic melanoma, who received irradiated autologous tumor cells as a vaccine. Two patients (SK-29 and MZ-2) with recurrent metastatic melanoma have been observed by our group since 1978 and 1982, respectively (Knuth et al. 1984). Both patients received intradermal immunization with irradiated autologous tumor cells for an extended period. Complete regression of tumor manifestations was documented after prolonged immunization with autologous tumor cells. The patients have now remained free of disease for 19 and 14 years, respectively. Based on the favorable clinical evolution in these cases, a systematic search was initiated to identify and characterize the cancer antigens and immune effector mechanisms mediating these tumor regressions in vivo (Knuth et al. 1991, 1992).