CXCR5 CAR-T cells simultaneously target B cell non-Hodgkin’s lymphoma and tumor-supportive follicular T helper cells

CAR-T cell therapy targeting CD19 demonstrated strong activity against advanced B cell leukemia, however shows less efficacy against lymphoma with nodal dissemination. To target both B cell Non-Hodgkin’s lymphoma (B-NHLs) and follicular T helper (Tfh) cells in the tumor microenvironment (TME), we ap...

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Autores principales: Bunse, Mario, Pfeilschifter, Janina, Bluhm, Julia, Zschummel, Maria, Joedicke, Jara J., Wirges, Anthea, Stark, Helen, Kretschmer, Vivien, Chmielewski, Markus, Uckert, Wolfgang, Abken, Hinrich, Westermann, Jörg, Rehm, Armin, Höpken, Uta E.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2021
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7801647/
https://www.ncbi.nlm.nih.gov/pubmed/33431832
http://dx.doi.org/10.1038/s41467-020-20488-3
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author Bunse, Mario
Pfeilschifter, Janina
Bluhm, Julia
Zschummel, Maria
Joedicke, Jara J.
Wirges, Anthea
Stark, Helen
Kretschmer, Vivien
Chmielewski, Markus
Uckert, Wolfgang
Abken, Hinrich
Westermann, Jörg
Rehm, Armin
Höpken, Uta E.
author_facet Bunse, Mario
Pfeilschifter, Janina
Bluhm, Julia
Zschummel, Maria
Joedicke, Jara J.
Wirges, Anthea
Stark, Helen
Kretschmer, Vivien
Chmielewski, Markus
Uckert, Wolfgang
Abken, Hinrich
Westermann, Jörg
Rehm, Armin
Höpken, Uta E.
author_sort Bunse, Mario
collection PubMed
description CAR-T cell therapy targeting CD19 demonstrated strong activity against advanced B cell leukemia, however shows less efficacy against lymphoma with nodal dissemination. To target both B cell Non-Hodgkin’s lymphoma (B-NHLs) and follicular T helper (Tfh) cells in the tumor microenvironment (TME), we apply here a chimeric antigen receptor (CAR) that recognizes human CXCR5 with high avidity. CXCR5, physiologically expressed on mature B and Tfh cells, is also highly expressed on nodal B-NHLs. Anti-CXCR5 CAR-T cells eradicate B-NHL cells and lymphoma-supportive Tfh cells more potently than CD19 CAR-T cells in vitro, and they efficiently inhibit lymphoma growth in a murine xenograft model. Administration of anti-murine CXCR5 CAR-T cells in syngeneic mice specifically depletes endogenous and malignant B and Tfh cells without unexpected on-target/off-tumor effects. Collectively, anti-CXCR5 CAR-T cells provide a promising treatment strategy for nodal B-NHLs through the simultaneous elimination of lymphoma B cells and Tfh cells of the tumor-supporting TME.
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spelling pubmed-78016472021-01-21 CXCR5 CAR-T cells simultaneously target B cell non-Hodgkin’s lymphoma and tumor-supportive follicular T helper cells Bunse, Mario Pfeilschifter, Janina Bluhm, Julia Zschummel, Maria Joedicke, Jara J. Wirges, Anthea Stark, Helen Kretschmer, Vivien Chmielewski, Markus Uckert, Wolfgang Abken, Hinrich Westermann, Jörg Rehm, Armin Höpken, Uta E. Nat Commun Article CAR-T cell therapy targeting CD19 demonstrated strong activity against advanced B cell leukemia, however shows less efficacy against lymphoma with nodal dissemination. To target both B cell Non-Hodgkin’s lymphoma (B-NHLs) and follicular T helper (Tfh) cells in the tumor microenvironment (TME), we apply here a chimeric antigen receptor (CAR) that recognizes human CXCR5 with high avidity. CXCR5, physiologically expressed on mature B and Tfh cells, is also highly expressed on nodal B-NHLs. Anti-CXCR5 CAR-T cells eradicate B-NHL cells and lymphoma-supportive Tfh cells more potently than CD19 CAR-T cells in vitro, and they efficiently inhibit lymphoma growth in a murine xenograft model. Administration of anti-murine CXCR5 CAR-T cells in syngeneic mice specifically depletes endogenous and malignant B and Tfh cells without unexpected on-target/off-tumor effects. Collectively, anti-CXCR5 CAR-T cells provide a promising treatment strategy for nodal B-NHLs through the simultaneous elimination of lymphoma B cells and Tfh cells of the tumor-supporting TME. Nature Publishing Group UK 2021-01-11 /pmc/articles/PMC7801647/ /pubmed/33431832 http://dx.doi.org/10.1038/s41467-020-20488-3 Text en © The Author(s) 2021 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/.
spellingShingle Article
Bunse, Mario
Pfeilschifter, Janina
Bluhm, Julia
Zschummel, Maria
Joedicke, Jara J.
Wirges, Anthea
Stark, Helen
Kretschmer, Vivien
Chmielewski, Markus
Uckert, Wolfgang
Abken, Hinrich
Westermann, Jörg
Rehm, Armin
Höpken, Uta E.
CXCR5 CAR-T cells simultaneously target B cell non-Hodgkin’s lymphoma and tumor-supportive follicular T helper cells
title CXCR5 CAR-T cells simultaneously target B cell non-Hodgkin’s lymphoma and tumor-supportive follicular T helper cells
title_full CXCR5 CAR-T cells simultaneously target B cell non-Hodgkin’s lymphoma and tumor-supportive follicular T helper cells
title_fullStr CXCR5 CAR-T cells simultaneously target B cell non-Hodgkin’s lymphoma and tumor-supportive follicular T helper cells
title_full_unstemmed CXCR5 CAR-T cells simultaneously target B cell non-Hodgkin’s lymphoma and tumor-supportive follicular T helper cells
title_short CXCR5 CAR-T cells simultaneously target B cell non-Hodgkin’s lymphoma and tumor-supportive follicular T helper cells
title_sort cxcr5 car-t cells simultaneously target b cell non-hodgkin’s lymphoma and tumor-supportive follicular t helper cells
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7801647/
https://www.ncbi.nlm.nih.gov/pubmed/33431832
http://dx.doi.org/10.1038/s41467-020-20488-3
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