Division of Pediatric Hematology/Oncology, Stanford University, Stanford, CA, USA.
Center for Cancer Cell Therapy, Stanford University, Stanford, CA, USA.
Leukemia. 2024 May;38(5):963-968. doi: 10.1038/s41375-024-02220-y. Epub 2024 Mar 15.
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.
嵌合抗原受体 (CAR) T 细胞靶向 CD22（CD22-CAR）为接受过 CD19 靶向治疗后进展的 CD22 恶性肿瘤患者提供了一种治疗选择。我们使用现场、自动化、闭环制造，在接受过大量治疗、复发/难治 (r/r) B-ALL 的儿童和成人中进行了平行的 1b 期临床试验，研究了一种具有 41BB 共刺激结构域的人源化 CD22-CAR。在纳入的 19 名患者中，18 名成功进行了 CD22-CAR 制造，16 名患者接受了输注。只有 1 名患者发生了 3-4 级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)；然而，有 3 名患者发生了免疫效应细胞相关噬血细胞性淋巴组织细胞增生症样综合征 (IEC-HS)。16 名患者中有 12 名 (75%) 达到了完全缓解，总完全缓解率为 56%，MRD 阴性。反应持续时间总体有限（中位数 77 天），在 4/12 例（33%）可获得的复发样本中 CD22 表达下调。总之，我们证明了闭环制造 CD22-CAR T 细胞是可行的，与儿科和成人 r/r B-ALL 患者中有利的安全性特征和高完全缓解率相关，该队列中 CD22-CAR 报告有限。
