The shaved tumor-specific antigen encoded by mouse gene P1A is a target not only for cytolytic T lymphocytes but also for tumor rejection

A number of human tumor antigens have been characterized recently using cyt olytic T lymphocytes (CTL) as screening tools. Some of them are encoded by MAGE-type genes, which are silent in normal tissues except in male germ cel ls, but are activated in a variety of tumors. These tumor-specific shared a ntigens appear to be promising targets for cancer immunotherapy. However, t he choice of these antigens as targets has been questioned because of the l ack of direct evidence that in vivo responses against such antigens can lea d to tumor rejection. The antigen encoded by the mouse gene PIA represents the only available animal model system for MAGE-type tumor antigens. We sho w here that mice immunized by injection of L1210 leukemia cells expressing P1A and B7-1 (L1210.P1A.B7-1) are efficiently protected against a challenge with a lethal dose of mastocytoma P815 tumor cells, which express P1A. Mic e immunized with L1210 cells expressing B7-1 but not PIA were not protected . Furthermore, we observed that PIA-transgenic mice, which are tolerant to P1A, were not protected after immunization with L1210.P1A.B7-1. These resul ts demonstrate that the immune response to P1A is the major component of th e tumor rejection response observed in normal mice, and support the use of tumor-specific shared antigens as targets for the immunotherapy of human ca ncer.