Silent CD24-engineered oncolytic virus vaccine enhances antitumor immunity.

Oncolytic virotherapy represents a highly promising in situ antitumor vaccine, using natural or engineered oncolytic viruses to specifically target and eradicate tumors. Malignant tumors overexpress the surface protein CD24, which signals "don't eat me" to inhibit macrophage phagocytosis of tumor cells. Oncolytic viruses are designed to express CD24 inhibitors to augment tumor elimination, serving as a potential antitumor vaccine for cancer immunotherapy. Therefore, we have developed an engineered oncolytic adenovirus that incorporates interfering RNA targeting CD24 for silencing (oAd-shCD24). The oAd-shCD24 vaccine induces sustained tumor suppression and long-term survival in tumor-bearing mice across various tumor models by inhibiting CD24 expression. Mechanistic analysis demonstrates that oAd-shCD24 increases the quantity of tumor-infiltrating immune cells that possess an activated immune phenotype while reducing the proportion of immunosuppressive cells, thus reshaping the tumor immune microenvironment. The combination of oAd-shCD24 with PD1 inhibitors shows superior antitumor efficacy. In summary, the oAd-shCD24 tumor vaccine exhibits effective antitumor efficacy and may represent a potential antitumor therapeutic agent.