Analysis of the principles underlying chemo-immunotherapy of mouse tumours

Summary

The nonspecific macrophage-mediated antitumour effects resulting from IV C. parvum (CP) in mice were resistant to cyclophosphamide (CY), whereas the specific T cell-mediated immunity resulting from SC injection of CP-irradiated tumour cell mixtures was sensitive for up to 8 days after immunisation, and resistant thereafter. Mice with solid fibrosarcoma (M4) were treated by IV CP followed by CY and, with intervals between CP and CY of 1–4 and 15–18 days, the antitumour effects of the CY were potentiated in a ‘synergistic’ manner. This did not happen with 8- or 12-day intervals. The most potent antitumour effects (39% complete regressions) occurred with the 15–18 day interval. (The antitumour activity of another alkylating agent, melphalan, was similarly potentiated when given 12–18 days after IV CP, but not after 4 days.) No potentiated antitumour effects were found when specific active immunotherapy with CP-irradiated tumour cell mixtures preceded CY by 1, 4, 8, 12, or 18 days. CP given IV increased the susceptibility of mice to subsequent high doses of CY, the peak sensitivity being around 10 days after CP.