MOUSE EMBRYO FIBROBLASTS TRANSFORMED BY ACTIVATED RAS OR DOMINANT-NEGATIVE P53 EXPRESS CROSS-REACTIVE TUMOR REJECTION ANTIGENS

To study the immune response against oncogene-transformed tumors, C3H/HeN mouse embryo fibroblasts (MEF) were transfected with an activated allele of the H-ras proto-oncogene Val12 and a dominant-negative allele of the murine p53 tumor suppressor gene Val135. Transformed cell lines were derived and found to be tumorigenic in syngeneic mice. Immunization with irradiated p53 + ras-transformed MEF, but not primary MEF or unrelated syngeneic cells, protected mice from subsequent challenge with live tumor cells. The role of different immune cell subsets in the effector phase of anti-tumor immunity induced by immunization with p53 + ras-transformed MEF was investigated by in vivo antibody depletion experiments. Immunized mice depleted of CD8(+) T, NK or B cells were resistant, but depletion of CD4(+) T cells rendered mice susceptible to tumorigenic challenge. In contrast to the tumor-specific immune responses mounted against most chemically or UV-induced tumors, a series of independently derived p53 + ras-transformed MEF were cross-reactive in tumor rejection assays. In addition, immunization with C3H-derived L-929 cell lines expressing single gene products H-ras or p53 did not protect mice against tumorigenic challenge with p53 + ras-transformed tumors. However, MEF transformed by expression of either H-ras or p53 were cross-protective in vivo. Our data suggest that the p53 + ras-transformed MEF share tumor rejection antigens which are also induced by single gene transformation of the parental primary cell but are not the products of oncogenic ras or p53 protein. (C) 1995 Wiley-Liss, Inc.