携带 CXCL11 的溶瘤腺病毒增强 CAR-T 细胞在胶质母细胞瘤中的治疗效果并重编程肿瘤微环境

Glioblastoma (GBM) is the most aggressive primary malignant brain cancer and urgently requires effective treatments. Chimeric antigen receptor T (CAR-T) cell therapy offers a potential treatment method, but it is often hindered by poor infiltration of CAR-T cells in tumors and highly immunosuppressive tumor microenvironment (TME).

Here, we armed an oncolytic adenovirus (oAds) with a chemokine CXCL11 to increase the infiltration of CAR-T cells and reprogram the immunosuppressive TME, thus improving its therapeutic efficacy. In both immunodeficient and immunocompetent orthotopic GBM mice models, we showed that B7H3-targeted CAR-T cells alone failed to inhibit GBM growth but, when combined with the intratumoral administration of CXCL11-armed oAd, it achieved a durable antitumor response.

Besides, oAd-CXCL11 had a potent antitumor effect and reprogramed the immunosuppressive TME in GL261 GBM models, in which increased infiltration of CD8 + T lymphocytes, natural killer (NK) cells, and M1-polarized macrophages, while decreased proportions of myeloid-derived suppressor cells (MDSCs), regulatory T cells (Tregs) and M2-polarized macrophages were observed.

Furthermore, the antitumor effect of the oAd-CXCL11 was CD8 + T cell dependent.

Our findings thus revealed that CXCL11-armed oAd can improve immune-virotherapy and can be a promising adjuvant of CAR-T therapy for GBM.