Previously, we had reported that a single i.p. injection of 15 mg
cyclophosphamide (CY) per kg cured most mice bearing large MOPC-315
tumors (20 to 25 mm; Day 12 to Day 16
tumors) but rarely cured mice bearing nonpalpable
tumors (Day 4
tumors). Also, mice that were not cured if treated with CY, 15 mg/kg, when they had nonpalpable
tumors could not be cured if treated again with CY, 15 mg/kg, when they had large
tumors (14). Here, we show that CY
therapy with 15 mg/kg at early stages of
tumor growth did not lead to alteration in the biology of the
tumor so as to cause an increased resistance to CY-tumoricidal effects, increased resistance to immune lysis, and/or decreased immunogenicity. Treatment of nonpalpable
tumor bearers with CY, 15 mg/kg, prior to in vitro immunization of their spleen cells did not reduce the ability of the spleen cells to generate antitumor cytotoxicity in vitro. However, the level of antitumor cytotoxicity generated was lower than that exhibited by in vitro-immunized spleen cells from mice treated with CY, 15 mg/kg, when they had large
tumors. With CY, 15 mg/kg, mice bearing nonpalpable
tumors could be cured in two ways: (a) by treating a mouse bearing a nonpalpable
tumor in the presence of a contralateral large
tumor; (b) by adoptive transfer of immune spleen cells given 1 day post-CY
therapy. Both procedures resulted in higher levels of antitumor immunity which was apparently responsible for the cure of the mice in cooperation with CY. Thus, the ineffectiveness of CY
therapy with 15 mg/kg at early stages of
tumor growth correlated with the presence of relatively low levels of host antitumor immunity.