Immunoprophylactic and immunotherapeutic response by concanavalin A-bound tumor vaccine enhanced by chemotherapeutic agents eliminating possible suppressors

Abstract

The combined administration of mitomycin C (MMC) on Day 5 and concanavalin A (Con A)-bound L1210 murine leukemia vaccine on Days 1 and 8 induced an enhanced therapeutic response in animals bearing L1210 leukemia greater than that inducible by either of them. The enhancement was dependent on the administration timing of the vaccine, dependent on vaccine-bound Con A, and specific for L1210 leukemia, as evidenced by the fact that no enhancement was induced in P388 leukemic animals. However, the enhancement was dependent on delayed MMC administration, and MMC administered on Day 3 failed to induce the enhancement, indicating that the chemotherapeutic potency of MMC played no major role in the enhancement. These results suggest that the enhancement may be dependent on antileukemia immunity induced by Con A-bound vaccine and may be further potentiated by MMC. A series of experiments comparing immunoprophylactic and immunotherapeutic responses inducible by different chemotherapeutic agents combined with the vaccine suggested that chemotherapeutic agents enhanced the potency of the vaccine by abrogating suppressors associated with vaccine-bound Con A. This hypothesis was supported by the finding that tumor vaccine induced peritoneal cells of tumor-bearing animals were abrogated in their suppressor activity in polyclonal in vitro spleen cell blastogenesis when these animals were further treated with MMC.