Cyclophosphamide and melphalan as immunopotentiating agents in cancer therapy

The murine plasmacytoma, MOPC-315, has been used as a tumor model to investigate the immunopotentiating effect of a low dose of cyclophosphamide (CY) or melphalan (L-PAM). Each drug was shown to shift the balance in mice bearing a late-stage tumor from a state of immunosuppression to that of potent T-cell-dependent antitumor immunity against tumor-associated antigens. The resultant immunity eradicated the extensive tumor burden not already eradicated by the direct tumoricidal activity of the drug and brought about the cure of the mice. The immunity responsible for tumor eradication, as well as the immunity responsible for the resistance of the cured mice to further tumor challenge, was mediated by the Lyt 2 subset of T-cells which contains cytotoxic T-cells. The principle of using a low dose of drug to selectively decrease suppressor cell activity so as to allow the development of antitumor immunity with the aid of autologous tumor vaccine or interleukin-2 has been exploited successfully by clinicians in therapeutic protocols for human melanoma.