靶向CD22的CAR-T细胞可使CD19 CAR治疗无效或未治的B细胞急性淋巴细胞白血病缓解
CD22-targeted CAR T cells induce remission in B-ALL that is naive or resistant to CD19-targeted CAR immunotherapy
靶向CD19的CAR-T细胞对复发难治的前体B细胞急性淋巴细胞白血病疗效显著，但抗原丢失是常见耐药原因；CD22在多数B细胞急性淋巴细胞白血病中也有表达，且CD19丢失后通常仍保留。这项1期试验在21名儿童和成人中测试新型CD22 CAR-T细胞，其中17人此前接受过CD19靶向免疫治疗。结果呈剂量依赖性抗白血病活性：接受每公斤体重≥1×10^6个CD22 CAR-T细胞的患者中73%（11/15）达到完全缓解，包括5例CD19低表达或无表达者；中位缓解期6个月。复发与CD22位点密度下降有关，提示抗原密度决定CAR功能。这是首次确立CD22 CAR-T在B细胞急性淋巴细胞白血病中的临床活性。
为什么推荐给您：首个CD22靶向CAR-T的人体试验，对CD19治疗耐药的白血病仍有效。
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摘要Abstract
Chimeric antigen receptor (CAR) T cells targeting CD19 mediate potent effects in relapsed and/or refractory pre-B cell acute lymphoblastic leukemia (B-ALL), but antigen loss is a frequent cause of resistance to CD19-targeted immunotherapy. CD22 is also expressed in most cases of B-ALL and is usually retained following CD19 loss. We report results from a phase 1 trial testing a new CD22-targeted CAR (CD22-CAR) in 21 children and adults, including 17 who were previously treated with CD19-directed immunotherapy. Dose-dependent antileukemic activity was observed, with complete remission obtained in 73% (11/15) of patients receiving ≥1 × 10^6 CD22-CAR T cells per kg body weight, including 5 of 5 patients with CD19dim or CD19- B-ALL. Median remission duration was 6 months. Relapses were associated with diminished CD22 site density that likely permitted CD22+ cell escape from killing by CD22-CAR T cells. These results are the first to establish the clinical activity of a CD22-CAR in B-ALL, including leukemia resistant to anti-CD19 immunotherapy, demonstrating potency against B-ALL comparable to that of CD19-CAR at biologically active doses. Our results also highlight the critical role played by antigen density in regulating CAR function.