CCL19-armed oncolytic adenovirus synergizes with CCR7-expressing CAR-T cells to suppress ovarian tumor growth.

Solid tumors remain refractory to chimeric antigen receptor (CAR) T cell therapy largely because they fail to infiltrate the tumor bed. We show that in vitro expanded HER2 CAR-T cells are more than 80% CCR7+ cells that migrate vigorously to CCL19. An E1B-55 kDa-deleted oncolytic adenovirus expressing CCL19 retained full oncolytic potency, secreted bioactive CCL19 and tripled CAR-T migration. In NSG mice bearing SKOV3 ovarian tumors, two intratumoral oAd-CCL19 injections followed by intravenous HER2-CAR-T cells achieved most effective inhibition of tumor growth without significant toxicity, accompanied by increased intratumoral CAR-T cells. Thus, CCL19-armed oncolytic adenovirus safely converts ovarian tumors into chemokine-rich targets that recruit CAR-T cells, providing a readily translatable strategy for solid-tumor CAR-T therapy.