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Treatment of Aggressive T Cell Lymphoblastic Lymphoma/leukemia Using Anti-CD5 CAR T Cells

While treatment for B-cell malignancies has been revolutionized through the advent of CAR immunotherapy, similar strategies for T-cell malignancies have been limited. Additionally, T-cell leukemias and lymphomas can commonly metastasize to the CNS, where outcomes are poor and treatment options are a...

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Autores principales: Feng, Jia, Xu, Haichan, Cinquina, Andrew, Wu, Zehua, Chen, Qi, Zhang, Ping, Wang, Xingen, Shan, Huiming, Xu, Lei, Zhang, Qian, Sun, Lihua, Zhang, Wenli, Pinz, Kevin G., Wada, Masayuki, Jiang, Xun, Hanes, William M, Ma, Yupo, Zhang, Hongyu
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer US 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8036178/
https://www.ncbi.nlm.nih.gov/pubmed/33410096
http://dx.doi.org/10.1007/s12015-020-10092-9
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author Feng, Jia
Xu, Haichan
Cinquina, Andrew
Wu, Zehua
Chen, Qi
Zhang, Ping
Wang, Xingen
Shan, Huiming
Xu, Lei
Zhang, Qian
Sun, Lihua
Zhang, Wenli
Pinz, Kevin G.
Wada, Masayuki
Jiang, Xun
Hanes, William M
Ma, Yupo
Zhang, Hongyu
author_facet Feng, Jia
Xu, Haichan
Cinquina, Andrew
Wu, Zehua
Chen, Qi
Zhang, Ping
Wang, Xingen
Shan, Huiming
Xu, Lei
Zhang, Qian
Sun, Lihua
Zhang, Wenli
Pinz, Kevin G.
Wada, Masayuki
Jiang, Xun
Hanes, William M
Ma, Yupo
Zhang, Hongyu
author_sort Feng, Jia
collection PubMed
description While treatment for B-cell malignancies has been revolutionized through the advent of CAR immunotherapy, similar strategies for T-cell malignancies have been limited. Additionally, T-cell leukemias and lymphomas can commonly metastasize to the CNS, where outcomes are poor and treatment options are associated with severe side effects. Consequently, the development of safer and more effective alternatives for targeting malignant T cells that have invaded the CNS remains clinically important. CD5 CAR has previously been shown to effectively target various T-cell cancers in preclinical studies. As IL-15 strengthens the anti-tumor response, we have modified CD5 CAR to secrete an IL-15/IL-15sushi complex. In a Phase I clinical trial, these CD5-IL15/IL15sushi CAR T cells were tested for safety and efficacy in a patient with refractory T-LBL with CNS infiltration. CD5-IL15/IL15sushi CAR T cells were able to rapidly ablate the CNS lymphoblasts within a few weeks, resulting in the remission of the patient’s lymphoma. Despite the presence of CD5 on normal T cells, the patient only experienced a brief, transient T-cell aplasia. These results suggest that CD5-IL15/IL15sushi CAR T cells may be a safe and useful treatment of T-cell malignancies and may be particularly beneficial for patients with CNS involvement. Graphical Abstract [Image: see text]
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spelling pubmed-80361782021-04-27 Treatment of Aggressive T Cell Lymphoblastic Lymphoma/leukemia Using Anti-CD5 CAR T Cells Feng, Jia Xu, Haichan Cinquina, Andrew Wu, Zehua Chen, Qi Zhang, Ping Wang, Xingen Shan, Huiming Xu, Lei Zhang, Qian Sun, Lihua Zhang, Wenli Pinz, Kevin G. Wada, Masayuki Jiang, Xun Hanes, William M Ma, Yupo Zhang, Hongyu Stem Cell Rev Rep Article While treatment for B-cell malignancies has been revolutionized through the advent of CAR immunotherapy, similar strategies for T-cell malignancies have been limited. Additionally, T-cell leukemias and lymphomas can commonly metastasize to the CNS, where outcomes are poor and treatment options are associated with severe side effects. Consequently, the development of safer and more effective alternatives for targeting malignant T cells that have invaded the CNS remains clinically important. CD5 CAR has previously been shown to effectively target various T-cell cancers in preclinical studies. As IL-15 strengthens the anti-tumor response, we have modified CD5 CAR to secrete an IL-15/IL-15sushi complex. In a Phase I clinical trial, these CD5-IL15/IL15sushi CAR T cells were tested for safety and efficacy in a patient with refractory T-LBL with CNS infiltration. CD5-IL15/IL15sushi CAR T cells were able to rapidly ablate the CNS lymphoblasts within a few weeks, resulting in the remission of the patient’s lymphoma. Despite the presence of CD5 on normal T cells, the patient only experienced a brief, transient T-cell aplasia. These results suggest that CD5-IL15/IL15sushi CAR T cells may be a safe and useful treatment of T-cell malignancies and may be particularly beneficial for patients with CNS involvement. Graphical Abstract [Image: see text] Springer US 2021-01-06 2021 /pmc/articles/PMC8036178/ /pubmed/33410096 http://dx.doi.org/10.1007/s12015-020-10092-9 Text en © The Author(s) 2021 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 licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence 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 licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Feng, Jia
Xu, Haichan
Cinquina, Andrew
Wu, Zehua
Chen, Qi
Zhang, Ping
Wang, Xingen
Shan, Huiming
Xu, Lei
Zhang, Qian
Sun, Lihua
Zhang, Wenli
Pinz, Kevin G.
Wada, Masayuki
Jiang, Xun
Hanes, William M
Ma, Yupo
Zhang, Hongyu
Treatment of Aggressive T Cell Lymphoblastic Lymphoma/leukemia Using Anti-CD5 CAR T Cells
title Treatment of Aggressive T Cell Lymphoblastic Lymphoma/leukemia Using Anti-CD5 CAR T Cells
title_full Treatment of Aggressive T Cell Lymphoblastic Lymphoma/leukemia Using Anti-CD5 CAR T Cells
title_fullStr Treatment of Aggressive T Cell Lymphoblastic Lymphoma/leukemia Using Anti-CD5 CAR T Cells
title_full_unstemmed Treatment of Aggressive T Cell Lymphoblastic Lymphoma/leukemia Using Anti-CD5 CAR T Cells
title_short Treatment of Aggressive T Cell Lymphoblastic Lymphoma/leukemia Using Anti-CD5 CAR T Cells
title_sort treatment of aggressive t cell lymphoblastic lymphoma/leukemia using anti-cd5 car t cells
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8036178/
https://www.ncbi.nlm.nih.gov/pubmed/33410096
http://dx.doi.org/10.1007/s12015-020-10092-9
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