Cargando…

Allogenic and autologous anti-CD7 CAR-T cell therapies in relapsed or refractory T-cell malignancies

Chimeric antigen receptor-T (CAR-T) therapy remains to be investigated in T-cell malignancies. CD7 is an ideal target for T-cell malignancies but is also expressed on normal T cells, which may cause CAR-T cell fratricide. Donor-derived anti-CD7 CAR-T cells using endoplasmic reticulum retention have...

Descripción completa

Detalles Bibliográficos
Autores principales: Zhang, Yinqiang, Li, Chenggong, Du, Mengyi, Jiang, Huiwen, Luo, Wenjing, Tang, Lu, Kang, Yun, Xu, Jia, Wu, Zhuolin, Wang, Xindi, Huang, Zhongpei, Zhang, Yanlei, Wu, Di, Chang, Alex H., Hu, Yu, Mei, Heng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10125858/
https://www.ncbi.nlm.nih.gov/pubmed/37095094
http://dx.doi.org/10.1038/s41408-023-00822-w
_version_ 1785030115628941312
author Zhang, Yinqiang
Li, Chenggong
Du, Mengyi
Jiang, Huiwen
Luo, Wenjing
Tang, Lu
Kang, Yun
Xu, Jia
Wu, Zhuolin
Wang, Xindi
Huang, Zhongpei
Zhang, Yanlei
Wu, Di
Chang, Alex H.
Hu, Yu
Mei, Heng
author_facet Zhang, Yinqiang
Li, Chenggong
Du, Mengyi
Jiang, Huiwen
Luo, Wenjing
Tang, Lu
Kang, Yun
Xu, Jia
Wu, Zhuolin
Wang, Xindi
Huang, Zhongpei
Zhang, Yanlei
Wu, Di
Chang, Alex H.
Hu, Yu
Mei, Heng
author_sort Zhang, Yinqiang
collection PubMed
description Chimeric antigen receptor-T (CAR-T) therapy remains to be investigated in T-cell malignancies. CD7 is an ideal target for T-cell malignancies but is also expressed on normal T cells, which may cause CAR-T cell fratricide. Donor-derived anti-CD7 CAR-T cells using endoplasmic reticulum retention have shown efficacy in patients with T-cell acute lymphoblastic leukemia (ALL). Here we launched a phase I trial to explore differences between autologous and allogeneic anti-CD7 CAR-T therapies in T-cell ALL and lymphoma. Ten patients were treated and 5 received autologous CAR-T therapies. No dose-limiting toxicity or neurotoxicity was observed. Grade 1–2 cytokine release syndrome occurred in 7 patients, and grade 3 in 1 patient. Grade 1–2 graft-versus-host diseases were observed in 2 patients. Seven patients had bone marrow infiltration, and 100% of them achieved complete remission with negative minimal residual disease within one month. Two-fifths of patients achieved extramedullary or extranodular remission. The median follow-up was 6 (range, 2.7–14) months and bridging transplantation was not administrated. Patients treated with allogeneic CAR-T cells had higher remission rate, less recurrence and more durable CAR-T survival than those receiving autologous products. Allogeneic CAR-T cells appeared to be a better option for patients with T-cell malignancies.
format Online
Article
Text
id pubmed-10125858
institution National Center for Biotechnology Information
language English
publishDate 2023
publisher Nature Publishing Group UK
record_format MEDLINE/PubMed
spelling pubmed-101258582023-04-26 Allogenic and autologous anti-CD7 CAR-T cell therapies in relapsed or refractory T-cell malignancies Zhang, Yinqiang Li, Chenggong Du, Mengyi Jiang, Huiwen Luo, Wenjing Tang, Lu Kang, Yun Xu, Jia Wu, Zhuolin Wang, Xindi Huang, Zhongpei Zhang, Yanlei Wu, Di Chang, Alex H. Hu, Yu Mei, Heng Blood Cancer J Article Chimeric antigen receptor-T (CAR-T) therapy remains to be investigated in T-cell malignancies. CD7 is an ideal target for T-cell malignancies but is also expressed on normal T cells, which may cause CAR-T cell fratricide. Donor-derived anti-CD7 CAR-T cells using endoplasmic reticulum retention have shown efficacy in patients with T-cell acute lymphoblastic leukemia (ALL). Here we launched a phase I trial to explore differences between autologous and allogeneic anti-CD7 CAR-T therapies in T-cell ALL and lymphoma. Ten patients were treated and 5 received autologous CAR-T therapies. No dose-limiting toxicity or neurotoxicity was observed. Grade 1–2 cytokine release syndrome occurred in 7 patients, and grade 3 in 1 patient. Grade 1–2 graft-versus-host diseases were observed in 2 patients. Seven patients had bone marrow infiltration, and 100% of them achieved complete remission with negative minimal residual disease within one month. Two-fifths of patients achieved extramedullary or extranodular remission. The median follow-up was 6 (range, 2.7–14) months and bridging transplantation was not administrated. Patients treated with allogeneic CAR-T cells had higher remission rate, less recurrence and more durable CAR-T survival than those receiving autologous products. Allogeneic CAR-T cells appeared to be a better option for patients with T-cell malignancies. Nature Publishing Group UK 2023-04-25 /pmc/articles/PMC10125858/ /pubmed/37095094 http://dx.doi.org/10.1038/s41408-023-00822-w Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Zhang, Yinqiang
Li, Chenggong
Du, Mengyi
Jiang, Huiwen
Luo, Wenjing
Tang, Lu
Kang, Yun
Xu, Jia
Wu, Zhuolin
Wang, Xindi
Huang, Zhongpei
Zhang, Yanlei
Wu, Di
Chang, Alex H.
Hu, Yu
Mei, Heng
Allogenic and autologous anti-CD7 CAR-T cell therapies in relapsed or refractory T-cell malignancies
title Allogenic and autologous anti-CD7 CAR-T cell therapies in relapsed or refractory T-cell malignancies
title_full Allogenic and autologous anti-CD7 CAR-T cell therapies in relapsed or refractory T-cell malignancies
title_fullStr Allogenic and autologous anti-CD7 CAR-T cell therapies in relapsed or refractory T-cell malignancies
title_full_unstemmed Allogenic and autologous anti-CD7 CAR-T cell therapies in relapsed or refractory T-cell malignancies
title_short Allogenic and autologous anti-CD7 CAR-T cell therapies in relapsed or refractory T-cell malignancies
title_sort allogenic and autologous anti-cd7 car-t cell therapies in relapsed or refractory t-cell malignancies
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10125858/
https://www.ncbi.nlm.nih.gov/pubmed/37095094
http://dx.doi.org/10.1038/s41408-023-00822-w
work_keys_str_mv AT zhangyinqiang allogenicandautologousanticd7cartcelltherapiesinrelapsedorrefractorytcellmalignancies
AT lichenggong allogenicandautologousanticd7cartcelltherapiesinrelapsedorrefractorytcellmalignancies
AT dumengyi allogenicandautologousanticd7cartcelltherapiesinrelapsedorrefractorytcellmalignancies
AT jianghuiwen allogenicandautologousanticd7cartcelltherapiesinrelapsedorrefractorytcellmalignancies
AT luowenjing allogenicandautologousanticd7cartcelltherapiesinrelapsedorrefractorytcellmalignancies
AT tanglu allogenicandautologousanticd7cartcelltherapiesinrelapsedorrefractorytcellmalignancies
AT kangyun allogenicandautologousanticd7cartcelltherapiesinrelapsedorrefractorytcellmalignancies
AT xujia allogenicandautologousanticd7cartcelltherapiesinrelapsedorrefractorytcellmalignancies
AT wuzhuolin allogenicandautologousanticd7cartcelltherapiesinrelapsedorrefractorytcellmalignancies
AT wangxindi allogenicandautologousanticd7cartcelltherapiesinrelapsedorrefractorytcellmalignancies
AT huangzhongpei allogenicandautologousanticd7cartcelltherapiesinrelapsedorrefractorytcellmalignancies
AT zhangyanlei allogenicandautologousanticd7cartcelltherapiesinrelapsedorrefractorytcellmalignancies
AT wudi allogenicandautologousanticd7cartcelltherapiesinrelapsedorrefractorytcellmalignancies
AT changalexh allogenicandautologousanticd7cartcelltherapiesinrelapsedorrefractorytcellmalignancies
AT huyu allogenicandautologousanticd7cartcelltherapiesinrelapsedorrefractorytcellmalignancies
AT meiheng allogenicandautologousanticd7cartcelltherapiesinrelapsedorrefractorytcellmalignancies