Efficacy and safety of humanized CD19 CAR‑T as a salvage therapy for recurrent CNSL of B‑ALL following murine CD19 CAR‑T cell therapy

Li,Xin; Liu,Mei-Jing; Mou,Nan; Yang,Zhen-Xing; Wang,Jia; Mu,Juan; Zhu,Hai-Bo; Deng,Qi

doi:10.3892/ol.2021.13049

Efficacy and safety of humanized CD19 CAR‑T as a salvage therapy for recurrent CNSL of B‑ALL following murine CD19 CAR‑T cell therapy

Authors:
- Xin Li
- Mei-Jing Liu
- Nan Mou
- Zhen-Xing Yang
- Jia Wang
- Juan Mu
- Hai-Bo Zhu
- Qi Deng
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Affiliations: Department of Hematology, Tianjin First Central Hospital, Tianjin 300192, P.R. China, Shanghai Genbase Biotechnology Co., Ltd., Tianjin 201210, P.R. China
Published online on: September 16, 2021 https://doi.org/10.3892/ol.2021.13049
Article Number: 788
Copyright: © Li et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

The present study aimed to compare the differences between the humanized CD19 chimeric antigen receptor (CAR)‑T cell therapy and the murine CD19 CAR‑T therapy in recurrent B‑acute lymphoblastic leukemia (B‑ALL). A 62‑year‑old male patient who had B‑ALL (BCR/ABL+) for 4 years was diagnosed with relapsed central nervous system leukemia (CNSL). After several courses of high dose methotrexate combined with intrathecal chemotherapy, the patient received murine CD19 CAR‑T therapy and achieved complete response (CR). The patient was diagnosed with relapsed CNSL again 15 months after his murine CD19 CAR‑T therapy, and was therefore enrolled in the humanized CD19 CAR‑T therapy. Subsequently, the present study aimed to compare murine and humanized CD19 CAR‑T cells against Nalm‑6 cells in vitro and in mice. The patient initially achieved CR from his murine CD19 CAR‑T therapy with Grade 1 cytokine‑release syndrome (CRS) and Grade 1 CAR‑T cell‑related encephalopathy syndrome (CRES). The patient then achieved CR again from his humanized CD19 CAR‑T therapy with Grade 1 CRS and Grade 2 CRES. Peak levels of CD19 CAR‑T cells were higher in humanized CD19 CAR‑T therapy than those in murine CD19 CAR‑T therapy 7 days after infusion in the peripheral blood, in bone marrow and in cerebrospinal fluid (CSF). The cytokine levels were higher in humanized CD19 CAR‑T therapy than those in murine CD19 CAR‑T therapy in the peripheral blood and in CSF. The cytotoxicity to Nalm‑6 cells was higher in humanized CD19 CAR‑T cells than that in murine CD19 CAR‑T cells in vitro. In Nalm‑6 BALB/c mice, the median survival time of mice in the murine CD19 CAR‑T group was 35 days, while it was 43 days in the humanized CD19 CAR‑T group. In conclusion, humanized CD19 CAR‑T cell therapy had a better curative effect than that of murine CD19 CAR‑T therapy, and may be used as a salvage treatment for recurrent B‑ALL after treatment with murine CD19 CAR‑T therapy.

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