Analysis of the principles underlying chemo-immunotherapy of mouse tumours

Summary A CBA mouse fibrosarcoma (M4) growing as a solid tumour was treated with a single high dose (200 mg/kg) of cyclophosphamide (CY) followed by C. parvum (CP) immunotherapy. The optimal time for the administration of both nonspecific (CP IV) and active specific (SC CP-irradiated tumour cell mixtures) immunotherapy after CY was 4 days, compared with 1, 8, or 12 days. Optimal combinations of CY and CP were synergistic in that they provided a stronger antitumour effect than the sum of the individual effects of the two agents. In keeping with the finding that a 4-day interval between CY and CP was better than only 1 day, studies in normal mice show that when CP is given early during the suppressive phase of CY the onset of both specific and nonspecific antitumour effects are delayed. CY increased the susceptibility of mice to the toxic effects of a subsequent high systemic dose of CP.