Serologic identification of multiple tumor-associated antigens on murine sarcomas

The humoral immune response to two transplanted chemically induced murine sarcomas (MCA-2 and MCA-3) was studied in C57BL/6N mice. These tumors were immunogenic as evidenced by tumor amputation and rechallenge experiments, and no cross-reactivity between them was observed in in vivo challenge experiments. Utilizing a complement-dependent microcytotoxicity assay, we detected antibody to both MCA-2 and MCA-3 in the sera of animals bearing MCA-3 as well as after tumor removal. The sera of animals hyperimmunized to MCA-3 (MCA-3HI) was also cytotoxic in high titer to both MCA-2 and MCA-3 (50% cytotoxicity titers of 1:80 and 1:320, respectively). Sequential absorptions of sera from animals bearing MCA-3 and MCA-3HI sera with fresh MCA-2 cells completely removed activity against MCA-2 but retained reactivity to MCA-3. Sequential absorptions with fresh MCA-3 cells produced stepwise reductions of activity against both tumors, whereas absorption with normal cells produced no loss of activity against either tumor. Thus both specific and cross-reactive antigens were expressed on the surfaces of MCA-3 cells. Only the specific tumor antigen appeared to be involved in in vivo protection against tumor challenge.