T cells redirected against Igβ for the immunotherapy of B cell lymphoma.
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| Abstract |
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.
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| Authors | Dongpeng Jiang, Xiaopeng Tian, Xiaosen Bian, Tingting Zhu, Huimin Qin, Ruixi Zhang, Yang Xu, Zhansheng Pan, Haiwen Huang, Jianhong Fu, Depei Wu, Jianhong Chu |
| Journal | Leukemia (Leukemia) Vol. 34 Issue 3 Pg. 821-830 (03 2020) ISSN: 1476-5551 [Electronic] England |
| PMID | 31624374 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't) |
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