By cloning in vitro we have obtained two sublines of the L5222 rat
leukemia, one with high (L5222-S) and the other with low (L5222-R) in vivo sensitivities to non-toxic doses of
mafosfamide, a stabilized derivative of 4-hydroxy-cyclophosphamide. This sensitivity in vivo was not related to the cytotoxic activity of the
drug in vitro. Treatment of rats bearing the L5222-S and of mice transplanted with the MOPC-315
plasmocytoma with low doses of
mafosfamide or
cyclophosphamide resulted in a high percentage of surviving animals, which were resistant to a subsequent
tumor challenge. Viable leukemic cells were needed to establish antitumor immunity, since it was not possible to induce resistance by injection of
mitomycin-C-treated, non-viable L5222 cells. The adoptive transfer of spleen cells from animals immune against the L5222-S and the MOPC-315 resulted in resistance of the syngeneic recipients against a rechallenge with
tumor cells, provided that the animals were treated with an immunosuppressive dose (100 mg/kg) of
cyclophosphamide prior to the spleen cell implantation. In nude mice treatment of the L5222 with low doses of
mafosfamide also resulted in surviving animals, however resistance to a second
tumor challenge occurred only sporadically. The data presented confirm that
therapy with
cyclophosphamide or
mafosfamide enhances host antitumor immunity but, contrary to previous reports, it could be demonstrated that successful
tumor rejection was independent of T cells.