Immunization against endogenous retroviral tumor-associated antigens

Endogenous retroviral gene products have been found in some human tumors, a nd therefore, may serve as antigens for immunotherapy approaches. The murin e colorectal carcinoma CT26 and melanoma B16 have recently been found to ex press the endogenous retroviral gene products gp70 and p15E, respectively, that can serve as antigens recognized by T cells. To date, though, there ha s been no demonstration of tumor treatment using an endogenous retroviral p rotein. In this study, we demonstrate that mice immunized with recombinant vaccinia encoding the gp70 H2-L-d-restricted minimal determinant were prote cted from CT26 tumor challenge. Splenocytes from mice immunized with vaccin ia gp70 specifically secreted IFN-gamma in response to gp70 peptide-pulsed stimulators. Although this strategy could protect against subsequent tumor challenge, it was ineffective against established tumors. Therefore, to inv estigate the treatment of established CT26 or B16 lung metastases, mice wer e treated with cultured dendritic cells (DCs) pulsed with gp70 or p15E pept ide. Significant inhibition of established lung metastases required immuniz ation with peptide-pulsed DCs pretreated with CD40 ligand that has been dem onstrated to increase the T-cell stimulatory activity of DCs. The ability t o immunize against endogenous retroviral tumor antigens may have relevance in the induction of antitumor immunity for some human cancers.