Non-Hodgkin lymphoma (NHL) is a common malignancy in the hematologic system, and traditional therapy has limited efficacy for people with recurrent/refractory NHL (R/R NHL), especially for patients with diffuse large B cell lymphoma (DLBCL). Chimeric antigen receptor (CAR) T-cell therapy is a novel and effective immunotherapy strategy for R/R hematopoietic malignancies, but relapses can occur due to the loss of CAR-T cells in vivo or the loss of antigen. One strategy to avoid antigen loss after CAR-T cell therapy is to target one more antigen simultaneously. Tandem CAR targeting CD19 and CD22 has demonstrated the reliability of tandem CAR-T cell therapy for R/R B-ALL. This study explores the therapeutic potential of tandem CD19/20 CAR-T in the treatment of R/R B cell NHL. The efficacy and safety of autologous CD19/20 CAR-T cells in eleven R/R B cell NHL adult patients were evaluated in an open-label, single-arm trial. Most patients achieved complete response, exhibiting the efficacy and safety of tandem CD19/20 CAR-T cells. The TCR repertoire diversity of CAR-T cells decreased after infusion. The expanded TCR clones in vivo were mainly derived from TCR clones that had increased expression of genes associated with immune-related signaling pathways from the infusion product (IP). The kinetics of CAR-T cells in vivo were linked to an increase in the expression of genes related to immune response and cytolysis/cytotoxicity.

非霍奇金淋巴瘤 （NHL） 是血液系统中常见的恶性肿瘤，传统疗法对复发/难治性 NHL （R/R NHL） 患者的疗效有限，尤其是对于弥漫性大 B 细胞淋巴瘤 （DLBCL） 患者。嵌合抗原受体 （CAR） T 细胞疗法是一种针对 R/R 造血系统恶性肿瘤的新型有效免疫治疗策略，但由于体内 CAR-T 细胞的丢失或抗原的丢失，可能会发生复发。避免 CAR-T 细胞治疗后抗原丢失的一种策略是同时靶向另一种抗原。靶向 CD19 和 CD22 的串联 CAR 已经证明了串联 CAR-T 细胞疗法治疗 R/R B-ALL 的可靠性。本研究探讨了串联 CD19/20 CAR-T 治疗 R/R B 细胞 NHL 的治疗潜力。在一项开放标签的单臂试验中评估了自体 CD19/20 CAR-T 细胞在 11 例 R/R B 细胞 NHL 成年患者中的疗效和安全性。大多数患者达到完全缓解，表现出串联 CD19/20 CAR-T 细胞的有效性和安全性。输注后 CAR-T 细胞的 TCR 库多样性降低。体内扩增的 TCR 克隆主要来源于输液产物 （IP） 中与免疫相关信号通路相关的基因表达增加的 TCR 克隆。CAR-T 细胞在体内的动力学与免疫反应和细胞溶解/细胞毒性相关基因表达的增加有关。