肿瘤细胞治疗研究
英文原题：A novel TanCAR targeting IL13Rα2 and EphA2 for enhanced glioblastoma therapy.
CAR-T 细胞疗法已被证明是对抗非实体瘤的有效策略；然而，CAR-T疗法对实体瘤（如胶质母细胞瘤）仍然是一个挑战。
CAR-T 细胞疗法已被证明是抗击非实体瘤的有效策略；然而，CAR-T疗法对于实体瘤（如胶质母细胞瘤）仍是一项挑战。为改进针对胶质母细胞瘤的CAR-T疗法，一种新型TanCAR被构建而成，其由IL13（4MS）和EphA2 scFv串联排列组成，并在体外和体内进行了验证。在体外，新型TanCAR重定向T细胞通过识别IL-13受体2（IL13R 2）或EphA2单独或同时遇到两个靶标时共同识别，杀死了胶质母细胞瘤肿瘤细胞，但未杀死仅携带IL13R 1/IL4R受体的正常细胞。作为进一步的原则验证，新型TanCAR在皮下胶质瘤异种移植小鼠模型中进行了测试。结果表明，新型TanCAR重定向T细胞比单一CAR-T细胞产生更大的胶质瘤肿瘤消退。因此，新型TanCAR重定向T细胞比单一IL13 CAR或EphA2 scFv CAR更有效、更有选择性地杀死胶质瘤，具有防止抗原逃逸和减少脱靶细胞毒性的潜力。
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 in vitro and in vivo. In vitro , the novel TanCAR-redirected T cells killed glioblastoma tumor cells by recognizing either IL-13 receptor 2 (IL13R 2) or EphA2 alone or together upon simultaneous encounter of both targets, but did not kill normal cells bearing only the IL13R 1/IL4R receptor. As further proof of principle, the novel TanCAR was tested in a subcutaneous glioma xenograft mouse model. The results indicated that the novel TanCAR-redirected T cells produced greater glioma tumor regression than single CAR-T cells. Thus, the novel TanCAR-redirected T cells kill gliomas more efficiently and selectively than a single IL13 CAR or EphA2 scFv CAR, with the potential for preventing antigen escape and reduced off-target cytotoxicity.
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