Co-immunization with IFI35 enhances the therapeutic effect of an adenovirus vaccine against renal carcinoma.

Interferon-induced protein 35 (IFI35), an immunomodulator, is highly expressed in tumor cells, yet its role in enhancing tumor vaccine efficacy remains unclear. In this study, an adenovirus (Ad) vaccine encoding dual targets, IFI35 and carbonic anhydrase IX (CAIX), was developed for renal carcinoma treatment. Co-immunization with Ad-IFI35/CAIX effectively inhibited tumor growth in a subcutaneous model and significantly increased the infiltration of CD8+ T cells and dendritic cells (DCs). Furthermore, Ad-IFI35/CAIX administration induced strong cytotoxic T lymphocyte (CTL) responses and expanded multifunctional CD8+ T cell populations. Depletion of CD8+ T cells abolished the vaccine's tumor regression effects, confirming that its therapeutic effect relies on CD8+ T cell-mediated immunity. In addition, Ad-IFI35/CAIX treatment enhanced the induction of memory CTL responses, effectively suppressing the growth of tumors implanted contralaterally. The Ad-IFI35/CAIX vaccine also elicited a strong CD8+ T cell-mediated immunity against tumor metastasis and growth in lung metastasis and orthotopic renal carcinoma models. These results indicate that the Ad vaccine dual targeting IFI35 and CAIX is a potential strategy for renal carcinoma treatment.