• Gang Heng, Jiankun Jia, Shiqi Li, Gang Fu, Meiling Wang, Dabing Qin, Yunyan Li, Li Pei, Xiaobo Tian, Jiasi Zhang, Yi Wu, Shali Xiang, Jia Wan, Wei Zhu, Pei Zhang, Qianzhen Zhang, Xi Peng, Linling Wang, Ping Wang, Zhihao Wei, Yingzi Zhang, Guiqin Wang, Xue Chen, Chengcheng Zhang, Yanni Sun, Wenxu Zhao, Yahan Fan, Zhi Yang, Jieping Chen, and Cheng Qian.
• Center of Biological Therapy, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China.
• Clin Cancer Res. 2020 Apr 1; 26 (7): 1606-1615.

PurposeImmunogenicity derived from the murine scFv, a major molecular compomemt of chimeric antigen receptors (CARs), may limit the persistence of CAR T cells, resulting in tumor relapse of patients in complete remission (CR). In this study, we developed a humanized anti-CD19 scFv CAR-T (hCAR-T) to treat patients with relapsed/refractory acute lymphoblastic leukemia (r/r ALL).Patients And MethodsIn this one-arm, open-labeled study, we infused the T cells modified with hCAR to patients with r/r ALL. Patients were evaluated with long-term follow-up for response and safety of the treatment. The study was registered at Clinicaltrials.gov (NCT02349698).ResultsTen patients with r/r ALL were recruited for this study. All were response evaluable and all achieved CR; eight patients remained CR, and six were in CR for over 18 months without further treatment. A long-term persistence of hCAR T cells was observed in most of the patients. Among these patients, four of them with high tumor burden and rapidly progressive disease (median, 58%) experienced grade 3-4 cytokine release syndrome (CRS) and neurotoxicity. These severe CRSs were successfully controlled by tocilizumab, glucocorticoid, and plasma exchange.ConclusionsT cells expressing the humanized anti-CD19 scFv CARs exhibited sustained therapeutic efficacy in the treatment of r/r ALL. Low replase rate was associated with the long-term persistence of CAR T cells.©2019 American Association for Cancer Research.

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