Cryo-Shocked Cancer Cells as an Oncolytic Adenovirus Reservoir for Glioblastoma Immunotherapy

Glioblastoma is the most common type of primary brain tumor, which has a high recurrence rate and a high mortality rate. Immunotherapy shows promise in cancer therapy due to its capacity to manipulate the immune system to attack tumor cells with less toxic and durable immune responses. However, the low immunogenicity and limited immune cell infiltration in a glioblastoma lead to a weakened antitumor immune response, resulting in suboptimal therapeutic efficacy. A compelling solution is provided by oncolytic adenovirus (OAs), which can selectively replicate within tumor cells while simultaneously promoting antitumor immunity. Herein, we constructed an oncolytic adenovirus reservoir (OAR) by shocking OA-loaded tumor cells in liquid nitrogen to eliminate proliferation and pathogenicity. OARs showed sustained OAs release and effectively lysed tumor cells in vitro and in vivo. In a mouse intracranial glioblastoma model, OARs could efficiently induce dendritic cells' maturation, facilitate the tumor recruitment, and promote the infiltration of cytotoxic effector T lymphocytes via a single treatment, resulting in specific antitumor immune responses and long-term animal survival. Taken together, these results demonstrated that OAR is a promising synergistic therapeutic strategy for treating glioblastoma.