Enhancement of leukemia rejection by mice successfully treated for L1210 leukemia due to low dose compared to high dose VP-16.

We have earlier shown that VP-16 combined with Cyclosporin A (CsA) produces tumor specific immunity to L1210 leukemia in BDF/1 mice [Slater LM, Sweet P, Stupecky M, Reynolds JT. Cyclosporin A/VP-16 produced immunity to L1210 leukemia: the participation of cytotoxic CD(8) T-lymphocytes, Clin Immunol Immunopathol 1995;75:239-45]. Our current studies, designed to determine the role of VP-16 independently of CsA in this effect show that increased dose intensity of VP-16, in the absence of CsA, improves the frequency of 60 day survival of treated mice but impairs the ability of 60 day surviving mice to reject L1210 leukemia challenge. This impairment is associated with progressive diminution of mitogen responses by spleen cells harvested from tumor free VP-16 treated mice.