Elimination of tumor-enhancing cells by cyclophosphamide and its relevance to cyclophosphamide therapy of the murine mammary tumor.
The antitumor effect of cyclophosphamide (CY) on a syngeneic mouse mammary tumor, MM46, was found to be due to selective elimination of host lymphoid cell populations as well as a direct cytotoxic effect of CY on tumor cells. marked inhibition of tumor growth after a single ip injection of CY on day 12 lasted for more than 3 weeks, unless the host was infused iv with spleen cells from tumor-bearing mice. The tumor-enhancing activity of spleen cells from tumor-bearing mice appeared to be mainly due to Thy 1.2 positive T lymphocytes and was no longer seen after CY treatment on day 12. The extent of tumor growth inhibition achieved with CY was critically dependent on the time of drug administration. CY had no antitumor effect when given before tumor inoculation. Associated with the antitumor effect of CY, augmentation of the antitumor delayed hypersensitivity reaction, or the cellular immune response, was observed. In contrast, the titer of antitumor antibody in the blood, or the humoral immune response, decreased. Cell transfer experiments showed that suppressor T cells for antitumor delayed hypersensitivity reaction specifically induced by the tumor inoculum were eliminated after CY treatment on day 12.
D000818:Animals; D002455:Cell Division / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D003520:Cyclophosphamide / Q000494:pharmacology / Q000627:therapeutic use*; D006968:Hypersensitivity, Delayed; D008214:Lymphocytes / Q000187:drug effects / Q000276:immunology*; D008264:Macrophages / Q000276:immunology; D008297:Male; D008325:Mammary Neoplasms, Experimental / Q000188:drug therapy / Q000276:immunology*; D051379:Mice; D008809:Mice, Inbred C3H; D013154:Spleen / Q000276:immunology
D003520:Cyclophosphamide