biostudies-literatureMuhammad NFundamental Research Funds for the Central UniversitiesShanxi Provincial Key Research and Development ProjectNational Natural Science Foundation of China729-741https://www.ebi.ac.uk/biostudies/studies/S-EPMC8908045biostudies-literatureUnknown24Chimeric antigen receptor T cell (CAR-T) therapy has been shown to be an effective strategy for combatting non-solid tumors; however, CAR-T therapy is still a challenge for solid tumors, such as glioblastoma. To improve CAR-T therapy for glioblastoma, a new TanCAR, comprising the tandem arrangement of IL13 (4MS) and EphA2 scFv, was generated and validated <i>in vitro</i> and <i>in vivo. In vitro</i>, the novel TanCAR-redirected T cells killed glioblastoma tumor cells by recognizing either IL-13 receptor α2 (IL13Rα2) or EphA2 alone or together upon simultaneous encounter of both targets, but did not kill normal cells bearing only the IL13Rα1/IL4Rα receptor. As further proof of principle, the novel TanCAR was tested in a subcutaneous glioma xenograft mouse model. The results indicated that tMolecular therapy oncolyticsA novel TanCAR targeting IL13Rα2 and EphA2 for enhanced glioblastoma therapy.PMC8908045GK2021070182018SF-10681773265SY20210003Muhammad NLi WXia HZheng XHu YWang RZhang ZMao QChang YZhao JfalseA novel TanCAR targeting IL13Rα2 and EphA2 for enhanced glioblastoma therapy.Chimeric antigen receptor T cell (CAR-T) therapy has been shown to be an effective strategy for combatting non-solid tumors; however, CAR-T therapy is still a challenge for solid tumors, such as glioblastoma. To improve CAR-T therapy for glioblastoma, a new TanCAR, comprising the tandem arrangement of IL13 (4MS) and EphA2 scFv, was generated and validated <i>in vitro</i> and <i>in vivo. In vitro</i>, the novel TanCAR-redirected T cells killed glioblastoma tumor cells by recognizing either IL-13 receptor α2 (IL13Rα2) or EphA2 alone or together upon simultaneous encounter of both targets, but did not kill normal cells bearing only the IL13Rα1/IL4Rα receptor. As further proof of principle, the novel TanCAR was tested in a subcutaneous glioma xenograft mouse model. The results indicated that t2022-01-01T00:00:00Z2022 Mar2025-04-19T09:25:27.981Z2025-04-19T09:25:27.981ZS-EPMC89080453531751310.1016/j.omto.2022.02.012