Correlation of in vitro and in vivo studies of antigens relevant to the control of murine breast cancer

Abstract

The specific immune response of C3H [mammary tumor virus (MTV)] (MTV+) and C3Hf sublines (MTV- or milk-MTV-) to mammary tumors of C3H origin was measured in vitro by the ability of lymphocytes derived from immunized animals to destroy 3H-proline prelabeled target cells after 36 hr of incubation in vitro (lymphocyte:target ratio, 400:1). Primary cytotoxic responses were obtained both in C3H and C3Hf mice and were mediated mainly by T-lymphocytes (Thy.1-positive cells). The degree of cross-reactivity between different C3H mammary tumors showed wide ranges and actually depended on the amounts of MTV-related antigens expressed in the tumor cells. An inverse relationship between MTV-related and H2 histocompatibility antigens was observed. Thy.1.2 antigen (theta-C3H) was also detected on the surface of mammary tumor cells. Both C3H and C3Hf recognized cross-reacting and noncross-reacting antigens in the tumor cells, although the magnitude of the response in the MTV+ mice was lower than in the C3Hf sublines. Soluble antigens could be extracted by 3 M KCl treatment of the tumor cells and could be used as immunogens (eliciting cytotoxic responses against mammary tumor cells), or as stimulators for thymidine uptake (blast transformation in vitro) for specifically immune T-lymphocytes. Attempts to modify spontaneous tumor development in C3H and C3HfA virgin female mice by immunization with formalinized MTV or with soluble antigens extracted from C3H mammary tumors, although still in progress, showed a moderate preventive effect (especially in the C3HfA) immunized with MTV and an acceleration of tumor appearance both in C3H and C3HfA mice immunized with the soluble antigens extracted from C3H mammary tumors. This last set of results, although preliminary, indicates that a better understanding of the immunological events in this system is essential for the design of experiments on prophylaxis of tumor development.