Chimeric antigen receptor (CAR) T cells targeting CD22 (CD22-CAR) provide a therapeutic option for patients with CD22⁺ malignancies with progression after CD19-directed therapies. Using on-site, automated, closed-loop manufacturing, we conducted parallel Phase 1b clinical trials investigating a humanized CD22-CAR with 41BB costimulatory domain in children and adults with heavily treated, relapsed/refractory (r/r) B-ALL. Of 19 patients enrolled, 18 had successful CD22-CAR manufacturing, and 16 patients were infused. High grade (3–4) cytokine release syndrome (CRS) and immune effector-cell-associated neurotoxicity syndrome (ICANS) each occurred in only one patient; however, three patients experienced immune-effector-cell-associated hemophagocytic lymphohistiocytosis-like syndrome (IEC-HS). Twelve of 16 patients (75%) achieved CR with an overall 56% MRD-negative CR rate. Duration of response was overall limited (median 77 days), and CD22 expression was downregulated in 4/12 (33%) available samples at relapse. In summary, we demonstrate that closed-loop manufacturing of CD22-CAR T cells is feasible and is associated with a favorable safety profile and high CR rates in pediatric and adult r/r B-ALL, a cohort with limited CD22-CAR reporting.

靶向 CD22 的嵌合抗原受体 (CAR) T 细胞 (CD22-CAR) 为CD19 定向治疗后病情进展的CD22 ^{+恶性肿瘤患者提供了一种治疗选择。}我们利用现场、自动化、闭环制造，进行了并行 1b 期临床试验，研究具有 41BB 共刺激域的人源化 CD22-CAR，用于治疗经过严格治疗的复发/难治性 (r/r) B-ALL 的儿童和成人。在入组的 19 名患者中，18 名成功制造了 CD22-CAR，16 名患者接受了输注。高级别（3-4）细胞因子释放综合征（CRS）和免疫效应细胞相关神经毒性综合征（ICANS）各仅发生在一名患者身上；然而，三名患者出现了免疫效应细胞相关噬血细胞性淋巴组织细胞增多症样综合征（IEC-HS）。16 名患者中有 12 名 (75%) 达到 CR，总体 MRD 阴性 CR 率为 56%。总体反应持续时间有限（中位 77 天），并且复发时 4/12 (33%) 可用样本中 CD22 表达下调。总之，我们证明 CD22-CAR T 细胞的闭环制造是可行的，并且与儿童和成人 r/r B-ALL（CD22-CAR 报告有限的队列）良好的安全性和高 CR 率相关。