Specificity of the generation and expression of enhanced anti-plasmacytoma immunity by spleen cells from melphalan-treated MOPC-315 tumor bearers

Summary We have shown previously that low-dose melphalan (L-PAM) therapy of mice bearing a large MOPC-315 plasmacytoma enables their hitherto immunosuppressed spleen cells to exert potent anti-MOPC-315 cytotoxicity following in vitro immunization with MOPC-315 tumor cells 3]. Here we show that, following in vitro immunization with MOPC-315 tumor cells, spleen cells from such L-PAM-treated MOPC-315 tumor bearers exhibited enhanced T-cell-mediated cytotoxicity not only against the MOPC-315 tumor, but also against another plasmacytoma (MOPC-104E) possessing surface immunoglobulin (SIg) of a different idiotype than the MOPC-315 cells, as well as against a variant of the MOPC-315 tumor which does not produce nor possess SIg (SIg^–MOPC-315). The enhanced cytotoxicity was directed against target antigens which are not expressed on the surface of the syngeneic WEHI 22.1 thymoma or the natural killer-sensitive YAC-1 cells. Plasmacytoma shared antigens, other than immunoglobulins, were able to stimulate spleen cells from L-PAM-cured MOPC-315 tumor bearers to generate in vitro a secondary type anti-plasmacytoma cytotoxic response. L-PAM-cured MOPC-315 tumor bearers exhibited in vivo immunity against SIg^–MOPC-315 tumor cells, which was sufficiently triggered by the SIg^– cells to bring about the rejection of a challenge of at least 100-fold the minimal lethal tumor dose of the SIg^–MOPC-315 cells. Thus, SIg^– MOPC-315 tumor cells present among SIg⁺ tumor cells in the parental MOPC-315 tumor inoculum 9, 26] can be eradicated in the L-PAM-treated MOPC-315 tumor bearers by the immune response to SIg⁺ tumor cells as well as by the immune response to SIg^– tumor cells themselves.Supported by Research Grant CA-35761 from the National Cancer Institute and Research Grant IM-435 from the American Cancer SocietyIn partial fulfillment of the requirements for the Doctor of Philosophy degree.