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Chimeric Antigen Receptor-Modified T Cell Immunotherapy for Relapsed and Refractory Adult Burkitt Lymphoma

Patients with Burkitt lymphoma who are refractory to initial therapy or who relapse after undergoing intensive chemotherapy and autologous stem cell transplantation (ASCT) usually have a poor prognosis. While there has been considerable progress in the use of chimeric antigen receptor-modified (CAR)...

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Autores principales: Wu, Jiaying, Cao, Yang, Zhang, Qi, Liu, Wanying, Zhou, Xiaoxi, Ming, Xi, Meng, Fankai, Zhang, Yicheng, Li, Chunrui, Huang, Liang, Wei, Jia, Zheng, Miao, Zhang, Shangkun, Zhang, Tongcun, Zhu, Xiaojian, Wang, Na, Wang, Jue, Wang, Gaoxiang, Zhou, Jianfeng, Liu, Bo, Xiao, Yi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9164136/
https://www.ncbi.nlm.nih.gov/pubmed/35669773
http://dx.doi.org/10.3389/fimmu.2022.879983
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author Wu, Jiaying
Cao, Yang
Zhang, Qi
Liu, Wanying
Zhou, Xiaoxi
Ming, Xi
Meng, Fankai
Zhang, Yicheng
Li, Chunrui
Huang, Liang
Wei, Jia
Zheng, Miao
Zhang, Shangkun
Zhang, Tongcun
Zhu, Xiaojian
Wang, Na
Wang, Jue
Wang, Gaoxiang
Zhou, Jianfeng
Liu, Bo
Xiao, Yi
author_facet Wu, Jiaying
Cao, Yang
Zhang, Qi
Liu, Wanying
Zhou, Xiaoxi
Ming, Xi
Meng, Fankai
Zhang, Yicheng
Li, Chunrui
Huang, Liang
Wei, Jia
Zheng, Miao
Zhang, Shangkun
Zhang, Tongcun
Zhu, Xiaojian
Wang, Na
Wang, Jue
Wang, Gaoxiang
Zhou, Jianfeng
Liu, Bo
Xiao, Yi
author_sort Wu, Jiaying
collection PubMed
description Patients with Burkitt lymphoma who are refractory to initial therapy or who relapse after undergoing intensive chemotherapy and autologous stem cell transplantation (ASCT) usually have a poor prognosis. While there has been considerable progress in the use of chimeric antigen receptor-modified (CAR) T cell immunotherapy for the treatment of relapsed and refractory (r/r) malignancies, explicit data on adult patients with r/r Burkitt lymphoma are limited. We conducted two single-arm clinical trials to evaluate the clinical efficacy and toxicity of CD19/CD22 CAR T cell immunotherapy both alone (trial A) and in combination with ASCT (trial B) in adult patients with r/r Burkitt lymphoma. In total, 28 adult patients with r/r Burkitt lymphoma were enrolled [trial A (n = 15) and trial B (n = 13)]. The median doses of CD22 and CD19 CAR T cell infusions were 4.1 × 10(6)/kg and 4.0 × 10(6)/kg, respectively. Subsequently, after CAR T cell infusion, overall and complete responses were observed in 19 (67.9%) and 16 (57.1%) patients, respectively. The cumulative incidence rates of grade 2–4 cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome were 39.3% (11/28) and 10.7% (3/28), respectively. After a median follow-up duration of 12.5 months, 16 patients (5 in trial A and 11 in trial B) survived. Both the estimated 1-year progression-free and overall survival rates were 55.6%. Our preliminary results indicated that salvage therapy with CD19/CD22 CAR T cell infusion alone and that in combination with ASCT are effective in treating some adult patients with r/r Burkitt lymphoma.
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spelling pubmed-91641362022-06-05 Chimeric Antigen Receptor-Modified T Cell Immunotherapy for Relapsed and Refractory Adult Burkitt Lymphoma Wu, Jiaying Cao, Yang Zhang, Qi Liu, Wanying Zhou, Xiaoxi Ming, Xi Meng, Fankai Zhang, Yicheng Li, Chunrui Huang, Liang Wei, Jia Zheng, Miao Zhang, Shangkun Zhang, Tongcun Zhu, Xiaojian Wang, Na Wang, Jue Wang, Gaoxiang Zhou, Jianfeng Liu, Bo Xiao, Yi Front Immunol Immunology Patients with Burkitt lymphoma who are refractory to initial therapy or who relapse after undergoing intensive chemotherapy and autologous stem cell transplantation (ASCT) usually have a poor prognosis. While there has been considerable progress in the use of chimeric antigen receptor-modified (CAR) T cell immunotherapy for the treatment of relapsed and refractory (r/r) malignancies, explicit data on adult patients with r/r Burkitt lymphoma are limited. We conducted two single-arm clinical trials to evaluate the clinical efficacy and toxicity of CD19/CD22 CAR T cell immunotherapy both alone (trial A) and in combination with ASCT (trial B) in adult patients with r/r Burkitt lymphoma. In total, 28 adult patients with r/r Burkitt lymphoma were enrolled [trial A (n = 15) and trial B (n = 13)]. The median doses of CD22 and CD19 CAR T cell infusions were 4.1 × 10(6)/kg and 4.0 × 10(6)/kg, respectively. Subsequently, after CAR T cell infusion, overall and complete responses were observed in 19 (67.9%) and 16 (57.1%) patients, respectively. The cumulative incidence rates of grade 2–4 cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome were 39.3% (11/28) and 10.7% (3/28), respectively. After a median follow-up duration of 12.5 months, 16 patients (5 in trial A and 11 in trial B) survived. Both the estimated 1-year progression-free and overall survival rates were 55.6%. Our preliminary results indicated that salvage therapy with CD19/CD22 CAR T cell infusion alone and that in combination with ASCT are effective in treating some adult patients with r/r Burkitt lymphoma. Frontiers Media S.A. 2022-05-20 /pmc/articles/PMC9164136/ /pubmed/35669773 http://dx.doi.org/10.3389/fimmu.2022.879983 Text en Copyright © 2022 Wu, Cao, Zhang, Liu, Zhou, Ming, Meng, Zhang, Li, Huang, Wei, Zheng, Zhang, Zhang, Zhu, Wang, Wang, Wang, Zhou, Liu and Xiao https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
Wu, Jiaying
Cao, Yang
Zhang, Qi
Liu, Wanying
Zhou, Xiaoxi
Ming, Xi
Meng, Fankai
Zhang, Yicheng
Li, Chunrui
Huang, Liang
Wei, Jia
Zheng, Miao
Zhang, Shangkun
Zhang, Tongcun
Zhu, Xiaojian
Wang, Na
Wang, Jue
Wang, Gaoxiang
Zhou, Jianfeng
Liu, Bo
Xiao, Yi
Chimeric Antigen Receptor-Modified T Cell Immunotherapy for Relapsed and Refractory Adult Burkitt Lymphoma
title Chimeric Antigen Receptor-Modified T Cell Immunotherapy for Relapsed and Refractory Adult Burkitt Lymphoma
title_full Chimeric Antigen Receptor-Modified T Cell Immunotherapy for Relapsed and Refractory Adult Burkitt Lymphoma
title_fullStr Chimeric Antigen Receptor-Modified T Cell Immunotherapy for Relapsed and Refractory Adult Burkitt Lymphoma
title_full_unstemmed Chimeric Antigen Receptor-Modified T Cell Immunotherapy for Relapsed and Refractory Adult Burkitt Lymphoma
title_short Chimeric Antigen Receptor-Modified T Cell Immunotherapy for Relapsed and Refractory Adult Burkitt Lymphoma
title_sort chimeric antigen receptor-modified t cell immunotherapy for relapsed and refractory adult burkitt lymphoma
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9164136/
https://www.ncbi.nlm.nih.gov/pubmed/35669773
http://dx.doi.org/10.3389/fimmu.2022.879983
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