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首页> 外文期刊>British Journal of Haematology >Synergistic and persistent effect of T-cell immunotherapy with anti-CD19 or anti-CD38 chimeric receptor in conjunction with rituximab on B-cell non-Hodgkin lymphoma
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Synergistic and persistent effect of T-cell immunotherapy with anti-CD19 or anti-CD38 chimeric receptor in conjunction with rituximab on B-cell non-Hodgkin lymphoma

机译：抗CD19或抗CD38嵌合受体联合利妥昔单抗对T细胞免疫疗法对B细胞非霍奇金淋巴瘤的协同和持续作用

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SummaryUsing artificial receptors, it is possible to redirect the specificity of immune cells to tumour-associated antigens, which is expected to provide a useful strategy for cancer immunotherapy. Given that B-cell non-Hodgkin lymphoma (B-NHL) cells invariably express CD19 and CD38, these antigens may be suitable molecular candidates for such immunotherapy. We transduced human peripheral T cells or a T-cell line with either anti-CD19-chimeric receptor (CAR) or anti-CD38-CAR, which contained an anti-CD19 or anti-CD38 antibody-derived single-chain variable domain respectively. Retroviral transduction led to anti-CD19-CAR or anti-CD38-CAR expression in T cells with high efficiency (>60%). The T cell line, Hut78, when transduced with anti-CD19-CAR or anti-CD38-CAR, exerted strong cytotoxicity against the B-NHL cell lines, HT and RL, and lymphoma cells isolated from patients. Interestingly, use of both CARs had an additive cytotoxic effect on HT cells in vitro. In conjunction with rituximab, human peripheral T cells expressing either anti-CD19-CAR or anti-CD38-CAR enhanced cytotoxicity against HT-luciferase cells in xenografted mice. Moreover, the synergistic tumour-suppressing activity was persistent in vivo for over 2 months. These results provide a powerful rationale for clinical testing of the combination of rituximab with autologous T cells carrying either CAR on aggressive or relapsed B-NHLs.
机译：总结使用人工受体，可以将免疫细胞的特异性重定向至肿瘤相关抗原，这有望为癌症免疫治疗提供有用的策略。鉴于B细胞非霍奇金淋巴瘤（B-NHL）细胞始终表达CD19和CD38，这些抗原可能是此类免疫疗法的合适分子候选物。我们用抗CD19嵌合受体（CAR）或抗CD38-CAR转导人外周血T细胞或T细胞系​​，它们分别包含抗CD19或抗CD38抗体衍生的单链可变域。逆转录病毒转导在T细胞中高效（> 60％）导致抗CD19-CAR或抗CD38-CAR表达。当用抗CD19-CAR或抗CD38-CAR转导时，T细胞系Hut78对B-NHL细胞系，HT和RL以及从患者中分离出的淋巴瘤细胞产生强大的细胞毒性。有趣的是，两种CAR的使用在体外对HT细胞都具有附加的细胞毒性作用。与利妥昔单抗结合，表达抗CD19-CAR或抗CD38-CAR的人外周T细胞增强了异种移植小鼠中针对HT荧光素酶细胞的细胞毒性。此外，协同的肿瘤抑制活性在体内持续超过2个月。这些结果为利妥昔单抗与在侵袭性或复发性B-NHL上携带CAR的自体T细胞组合的临床测试提供了强有力的理论依据。

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