CD19-targeted chimeric antigen receptor-T (CAR-T) cells with CD28 or 4-1BB (28z CAR-T and BBz CAR-T) have shown great promise to treat relapsed or refractory (r/r) B cell non-Hodgkin’s lymphoma (B-NHL). However, comparison of their clinical outcomes has never been reported. This study investigated their efficacy and adverse events in B-NHL therapy. Six patients with r/r B-NHL were initially enrolled and infused with 28z or BBz CAR-T cells at a dose of 0.75–5 × 10⁵/kg. These CAR-T cells showed similar antitumor efficacies, with a complete response (CR) rate of 67% within 3 months. BBz CAR-T was well tolerated. However, severe cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome occurred in the 28z CAR-T cohort, resulting in the termination of further evaluation of 28z CAR-T. Three more patients were enrolled to investigate BBz CAR-T cells in-depth at an escalated dose (1 × 10⁶/kg). All cases achieved CR within 3 months, and only grade 1/2 adverse events occurred. This study suggests that 4-1BB is more beneficial for the clinical performance of CAR-T cells than CD28 in CD19-targeted B-NHL therapy, at least under our manufacturing process.

具有CD28或4-1BB（28z CAR-T和BBz CAR-T）的CD19靶向嵌合抗原受体T细胞（CAR-T）已显示出治疗非复发性或难治性（r / r）B细胞非霍奇金氏病的巨大希望淋巴瘤（B-NHL）。但是，尚未对其临床结果进行比较。这项研究调查了他们在B-NHL治疗中的疗效和不良事件。最初招募了6名r / r B-NHL患者，并以0.75-5×10 ⁵的剂量注入28z或BBz CAR-T细胞/公斤。这些CAR-T细胞显示出相似的抗肿瘤功效，在3个月内的完全缓解率（CR）为67％。BBz CAR-T的耐受性良好。但是，在28z CAR-T队列中发生了严重的细胞因子释放综合征和免疫效应细胞相关的神经毒性综合征，导致对28z CAR-T的进一步评估终止。招募了另外三名患者以递增剂量（1×10 ⁶ / kg）深入研究BBz CAR-T细胞。所有病例均在3个月内达到CR，仅发生1/2级不良事件。这项研究表明，至少在我们的制造过程中，在CD19靶向的B-NHL治疗中，4-1BB比CD28更有益于CAR-T细胞的临床表现。