Enable CAR T cell immunotherapy in glioblastoma by modifying its microenvironment via oncolytic adenovirus encoding bispecific T cell engager.

. Moreover, OV-BiTE treatment also markedly enhanced CAR T cell infiltration and tumor cytotoxicity in a GBM-BBB spheroid model, possibly through downregulation of endothelial junction protein expression. We then showed that intratumoral injection of OV-BiTE followed by infusion of combined EGFR and EGFRvIII CAR T cells was more effective than OV-BiTE supplemented with either CAR T therapy alone and led to significant tumor reduction in a GBM xenograft mouse model. In conclusion, our multimodal OV-BiTE plus CAR T cell immunotherapy is capable of overcoming the immunosuppressive tumor microenvironment and GBM resistance to treatment.