肿瘤细胞治疗研究
英文原题：Multispecific CAR T Cells Deprive Lymphomas of Escape via Antigen Loss.
Multispecific CAR T Cells Deprive Lymphomas of Escape via Antigen Loss.
嵌合抗原受体（CAR）修饰的T细胞疗法已经改变了复发/难治性B细胞恶性肿瘤的治疗格局。
嵌合抗原受体（CAR）修饰的T细胞疗法已经改变了复发/难治性B细胞恶性肿瘤的治疗格局。尽管总体缓解率很高，但CAR T治疗后的复发仍然是一个临床挑战。靶抗原丢失，特别是CD19丢失，是疾病复发的一个明确机制。CD19丢失的机制以及哪些患者面临更高的CD19丢失风险，目前仍知之甚少。为了克服CD19丢失，靶向多种抗原的CAR正在临床试验中进行测试。CD19/20和CD19/22双特异性CAR在临床前研究中显示出对CD19阴性细胞的细胞毒性。这些CAR在I期试验中也显示出疗效、安全性以及相对较低的CD19阴性复发率。这些小规模研究表明，多特异性CAR T细胞可以剥夺淋巴瘤通过抗原丢失逃逸的能力。然而，理想靶点的选择、正确的CAR构建体，以及这些多特异性CAR能否诱导长期缓解，仍在研究中。
Chimeric antigen receptor (CAR) modified T cell therapy has transformed the management of relapsed/refractory B cell malignancies. Despite high overall response rates, relapse post CAR T treatment remains a clinical challenge. Loss of target antigen, specifically CD19, is one well-defined mechanism of disease relapse. The mechanism of CD19 loss and which patients are at higher risk of CD19 loss remain poorly understood. To overcome CD19 loss, CARs targeting multiple antigens are being tested in clinical trials. CD19/20 and CD19/22 bispecific CARs demonstrate cytotoxicity against CD19-negative cells in preclinical studies. These CARs have also shown efficacy, safety, and a relatively low rate of CD19-negative relapse in phase I trials. These small studies suggest that multispecific CAR T cells can deprive lymphomas of escape via antigen loss. However, the selection of an ideal target, the right CAR construct, and whether these multispecific CARs can induce long-term remissions are still under investigation.
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