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）是血液系统常见恶性肿瘤，传统治疗对于复发/难治性NHL（R/R NHL）患者疗效有限，尤其对弥漫大B细胞淋巴瘤（DLBCL）患者而言。嵌合抗原受体（CAR）T细胞疗法是针对R/R血液系统恶性肿瘤的新型有效免疫治疗策略，但可能因体内CAR-T细胞丢失或抗原丢失而导致复发。一种避免CAR-T细胞治疗后抗原丢失的策略是同时靶向多个抗原。靶向CD19和CD22的双特异性CAR已在R/R B-ALL治疗中证明了其可靠性。本研究探索了CD19/20双特异性CAR-T治疗R/R B细胞NHL的潜在疗效。通过一项开放标签、单臂试验，评估了11例R/R B细胞NHL成年患者接受自体CD19/20 CAR-T细胞治疗的有效性和安全性。大多数患者获得完全缓解，显示出CD19/20双特异性CAR-T细胞疗法的有效性和安全性。输注后CAR-T细胞的TCR谱系多样性降低。体内扩增的TCR克隆主要来源于输注产品（IP）中免疫相关信号通路基因表达增强的TCR克隆。CAR-T细胞在体内的动力学变化与免疫应答及细胞溶解/细胞毒性相关基因表达上调密切相关。
肿瘤(癌症)患者之家