T cells redirected against Igβ for the immunotherapy of B cell lymphoma
T cells redirected against Igβ for the immunotherapy of B cell lymphoma
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T 细胞针对 Igβ 进行重定向，用于 B 细胞淋巴瘤的免疫治疗
DOI：
10.1038/s41375-019-0607-5
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发表时间：
2020-03-01
期刊：
影响因子：
11.4
通讯作者：
Chu, Jianhong
中科院分区：
文献类型：
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作者：
Jiang, Dongpeng;Tian, Xiaopeng;Chu, Jianhong
CD 19重定向的CAR-T免疫疗法已成为治疗B细胞淋巴瘤的一种有前景的策略，然而，许多患者经常因抗原丢失而复发。因此，迫切需要探索CAR-T细胞靶向的其他合适抗原，以治愈B细胞淋巴瘤。IGβ是B细胞受体（BCR）复合物的一种成分，在淋巴瘤细胞表面高度表达。在本研究中，我们设计了表达抗IG β CAR的T细胞，并观察到IGβ-CAR T细胞可以在体外和两种不同的淋巴瘤异种移植模型中有效地识别和清除IGβ+淋巴瘤细胞。通过野生型或突变型IGβ基因转导以及靶细胞中的IGβ特异性敲除，进一步证实了IGβ-CAR T细胞的特异性。值得注意的是，IGβ CAR-T细胞的体外和体内作用均与CD 19 CAR-T细胞相当。重要的是，在自体环境中，IGβ CAR-T细胞识别并根除患者来源的淋巴瘤细胞。最后，抗Ig β CAR-T细胞的安全性可以通过引入诱导型caspase-9自杀基因系统进一步增强。总的来说，IGβ特异性CAR-T细胞可能是治疗B细胞淋巴瘤的一种有前途的免疫治疗方法。
CD19-redirected CAR-T immunotherapy has emerged as a promising strategy for treatment of B cell lymphoma, however, many patients often relapsed due to antigen loss. Therefore, it is urgently needed to explore other suitable antigens targeted by CAR-T cells to cure B cell lymphoma. Igβ is a component of the B cell receptor (BCR) complex, which is highly expressed on the surface of lymphoma cells. In this study, we engineered T cells to express anti-Igβ CAR with CD28 costimulatory signaling moiety and observed that Igβ-CAR T cells could efficiently recognize and eliminate Igβ+lymphoma cells both in vitro and in two different lymphoma xenograft models. The specificity of Igβ-CAR T cells was further confirmed through wild type or mutated Igβ gene transduction together with Igβ-specific knockout in target cells. Of note, both the in vitro and in vivo effect of Igβ CAR-T cells was comparable with that of CD19 CAR-T cells. Importantly, Igβ CAR-T cells recognized and eradicated patient-derived lymphoma cells in the autologous setting. Lastly, the safety of anti-Igβ CAR-T cells could be further enhanced by introduction of the inducible caspase-9 suicide gene system. Collectively, Igβ-specific CAR-T cells may be a promising immunotherapeutic approach for B cell lymphoma.