Cooperation between cyclophosphamide tumoricidal activity and host antitumor immunity in the cure of mice bearing large MOPC-315 tumors.

A single i.p. injection of cyclophosphamide (CY), 15 mg/kg, was shown previously to be curative if administered to BALB/c mice 10 to 16 days post-MOPC-315 tumor inoculation when the tumors reached 20 to 25 mm (large tumors) but not if administered to mice four days post-tumor inoculation when their tumors were nonpalpable. Here we show that the curative effect of CY, 15 mg/kg, for mice bearing large tumors was not due solely to the tumoricidal activity of the drug, because three or four days after therapy, when the CY had been cleared from the circulation, viable proliferative tumor cells were present in the primary s.c. tumor site. During tumor regression, the tumors became heavily infiltrated by mononuclear cells. Following therapy, mice bearing large tumors exhibited an active antitumor response, as illustrated by their ability to reject a tumor challenge with 350-fold the minimum lethal tumor dose given as early as 24 hr posttherapy. That the curative effect of CY, 15 mg/kg, for mice bearing large tumors required the presence of T-cell-dependent antitumor immunity (cellular and/or humoral), was indicated by the fact that tumor regression was abrogated by treatment of the tumor bearers with anti-thymocyte serum. Thus, CY drug tumoricidal activity and host antitumor immunity cooperated in the eradication of large MOPC-315 tumors.