Previous experiments in the chemotherapy of plasmacytoma LPC-1 in syngeneic BALB/c mice revealed a correlation between the effectiveness of the drug or drug combination and the proportion of mice subsequently immune to tumor challenge. Additional parameters were examined to clarify this observation and to determine which immune mechanism(s) were involved in drug-initiated immunity. The magnitude of the rejection response to LPC-1 in mice cured of LPC-1 was high. The 50% tumor-producing dose in cured mice was 106.5 compared with 101.5 in normal mice, a resistance ratio of 105. Duration of immunity decreased with time, from 90 to 100% survivors at 4 months to <50% at 7 to 12 months, and decreased with increasing size of challenge dose. Immunity of cured mice to LPC-1 was highly specific for LPC-1 (85% survivors) and partially specific for plasmacytoma ADJ-PC-5 (29% survivors). The cured mice were not immune to two other plasmacytomas and a sarcoma, all syngeneic with BALB/c. In assays for cell-mediated cytotoxicity, peritoneal exudate but not spleen or lymph node cells were cytolytic to 51Cr-labeled LPC-1 target cells from cured mice after challenge with mitomycin C-treated LPC-1. Lymphoid cells from cured, unchallenged mice were inactive. Time studies of cell-mediated cytotoxicity using peritoneal exudate cells from LPC-1-implanted mice before, during, and after therapy with 5-fluorouracil revealed 2 major peaks of cytolysis, on Days 18 and 77. Treatment of lymphocytes with anti-Thy 1.2 plus complement destroyed all cytolytic activity. In all experiments, complement-dependent cytotoxicity in sera was absent. These observations suggest that destruction of residual tumor cells after chemotherapeutically induced regression may be due to specific immunological responses.


This investigation was supported in part by Grants CA-18256 and CA-16271 and by Core Grant CA-08748, awarded by the National Cancer Institute, Department of Health, Education, and Welfare. Presented, in part, at the 67th Annual Meeting of the American Association for Cancer Research, Toronto, Ontario, Canada, May 4 to 8, 1976 (21).

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