嵌合抗原受体（CAR）改造的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方式。尽管总体反应率高，但CAR T治疗后的复发仍然是一个临床挑战。目标抗原，特别是CD19的丢失是疾病复发的一个被明确定义的机制。CD19的丢失机制以及哪些患者具有较高的CD19丢失的风险仍然不太清楚。为了克服CD19的丢失，CARs针对多种抗原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还在I期试验中显示出疗效、安全性和相对较低的CD19阴性复发率。这些小型研究表明，多特异性CAR T细胞可以通过抗原丢失剥夺淋巴瘤的逃逸。然而，选择理想的靶点，正确的CAR构造，以及这些多特异性CARs是否能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.