T-cell-mediated antitumor immune response induced by oncofetal antigens

The possibility that fetal antigens take part in tumor immunity has been investigated to a limited extent, but the results of these studies have been controversial. It is not clear that tumor inhibition shown in some systems is due to an immune reaction. In the present study, performed in a weakly immunogenic tumor system (Lewis T241 fibrosarcoma in inbred C57BL/6J mice), immunization of mice with syngeneic fetal cells resulted in striking inhibition of growth and metastases of tumors. Mice that had gone through single pregnancies also showed a decreased rate of tumor growth and tumor metastases. Further studies have shown that the tumor inhibitory response evoked by fetal cell immunization is due to fetal antigens, and the male specific HY antigen is not responsible for antitumor response. Injection of tumor cells mixed with spleen cells from mice immunized with syngeneic fetal cells into normal mice resulted in significant inhibition of tumor growth and metastases in the Winn neutralization assay. Syngeneic fetal cells, normal adult spleen cells, or spleen cells from C57BL/6 mice immunized with allogeneic fetal cells did not inhibit tumor growth or metastases. These results show that tumor inhibition following fetal cell immunization is due to an immune reaction and is not due to a nonimmune physiologic process. Further analysis of effector cells showed them to be of the T-cell type.