ELIMINATION OF TUMOR-ENHANCING CELLS BY CYCLOPHOSPHAMIDE AND ITS RELEVANCE TO CYCLOPHOSPHAMIDE THERAPY OF A MURINE MAMMARY-TUMOR

  • 1 January 1981
    • journal article
    • research article
    • Vol. 72  (5) , 723-731
Abstract
The antitumor effect of cyclophosphamide (CY) on a syngeneic mouse mammary tumor, MM46, was due to selective elimination of host lymphoid cell populations and a direct cytotoxic effect of CY on tumor cells. Marked inhibition of tumor growth after a single i.p. injection of CY on day 12 lasted for > 3 wk, unless the host was infused i.v. 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 tumor inoculum were eliminated after CY treatment on day 12.