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A BAFF ligand-based CAR-T cell targeting three receptors and multiple B cell cancers

B cell-activating factor (BAFF) binds the three receptors BAFF-R, BCMA, and TACI, predominantly expressed on mature B cells. Almost all B cell cancers are reported to express at least one of these receptors. Here we develop a BAFF ligand-based chimeric antigen receptor (CAR) and generate BAFF CAR-T...

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Autores principales: Wong, Derek P., Roy, Nand K., Zhang, Keman, Anukanth, Anusha, Asthana, Abhishek, Shirkey-Son, Nicole J., Dunmire, Samantha, Jones, Bryan J., Lahr, Walker S., Webber, Beau R., Moriarity, Branden S., Caimi, Paolo, Parameswaran, Reshmi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8752722/
https://www.ncbi.nlm.nih.gov/pubmed/35017485
http://dx.doi.org/10.1038/s41467-021-27853-w
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author Wong, Derek P.
Roy, Nand K.
Zhang, Keman
Anukanth, Anusha
Asthana, Abhishek
Shirkey-Son, Nicole J.
Dunmire, Samantha
Jones, Bryan J.
Lahr, Walker S.
Webber, Beau R.
Moriarity, Branden S.
Caimi, Paolo
Parameswaran, Reshmi
author_facet Wong, Derek P.
Roy, Nand K.
Zhang, Keman
Anukanth, Anusha
Asthana, Abhishek
Shirkey-Son, Nicole J.
Dunmire, Samantha
Jones, Bryan J.
Lahr, Walker S.
Webber, Beau R.
Moriarity, Branden S.
Caimi, Paolo
Parameswaran, Reshmi
author_sort Wong, Derek P.
collection PubMed
description B cell-activating factor (BAFF) binds the three receptors BAFF-R, BCMA, and TACI, predominantly expressed on mature B cells. Almost all B cell cancers are reported to express at least one of these receptors. Here we develop a BAFF ligand-based chimeric antigen receptor (CAR) and generate BAFF CAR-T cells using a non-viral gene delivery method. We show that BAFF CAR-T cells bind specifically to each of the three BAFF receptors and are effective at killing multiple B cell cancers, including mantle cell lymphoma (MCL), multiple myeloma (MM), and acute lymphoblastic leukemia (ALL), in vitro and in vivo using different xenograft models. Co-culture of BAFF CAR-T cells with these tumor cells results in induction of activation marker CD69, degranulation marker CD107a, and multiple proinflammatory cytokines. In summary, we report a ligand-based BAFF CAR-T capable of binding three different receptors, minimizing the potential for antigen escape in the treatment of B cell cancers.
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spelling pubmed-87527222022-01-20 A BAFF ligand-based CAR-T cell targeting three receptors and multiple B cell cancers Wong, Derek P. Roy, Nand K. Zhang, Keman Anukanth, Anusha Asthana, Abhishek Shirkey-Son, Nicole J. Dunmire, Samantha Jones, Bryan J. Lahr, Walker S. Webber, Beau R. Moriarity, Branden S. Caimi, Paolo Parameswaran, Reshmi Nat Commun Article B cell-activating factor (BAFF) binds the three receptors BAFF-R, BCMA, and TACI, predominantly expressed on mature B cells. Almost all B cell cancers are reported to express at least one of these receptors. Here we develop a BAFF ligand-based chimeric antigen receptor (CAR) and generate BAFF CAR-T cells using a non-viral gene delivery method. We show that BAFF CAR-T cells bind specifically to each of the three BAFF receptors and are effective at killing multiple B cell cancers, including mantle cell lymphoma (MCL), multiple myeloma (MM), and acute lymphoblastic leukemia (ALL), in vitro and in vivo using different xenograft models. Co-culture of BAFF CAR-T cells with these tumor cells results in induction of activation marker CD69, degranulation marker CD107a, and multiple proinflammatory cytokines. In summary, we report a ligand-based BAFF CAR-T capable of binding three different receptors, minimizing the potential for antigen escape in the treatment of B cell cancers. Nature Publishing Group UK 2022-01-11 /pmc/articles/PMC8752722/ /pubmed/35017485 http://dx.doi.org/10.1038/s41467-021-27853-w Text en © The Author(s) 2022 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
Wong, Derek P.
Roy, Nand K.
Zhang, Keman
Anukanth, Anusha
Asthana, Abhishek
Shirkey-Son, Nicole J.
Dunmire, Samantha
Jones, Bryan J.
Lahr, Walker S.
Webber, Beau R.
Moriarity, Branden S.
Caimi, Paolo
Parameswaran, Reshmi
A BAFF ligand-based CAR-T cell targeting three receptors and multiple B cell cancers
title A BAFF ligand-based CAR-T cell targeting three receptors and multiple B cell cancers
title_full A BAFF ligand-based CAR-T cell targeting three receptors and multiple B cell cancers
title_fullStr A BAFF ligand-based CAR-T cell targeting three receptors and multiple B cell cancers
title_full_unstemmed A BAFF ligand-based CAR-T cell targeting three receptors and multiple B cell cancers
title_short A BAFF ligand-based CAR-T cell targeting three receptors and multiple B cell cancers
title_sort baff ligand-based car-t cell targeting three receptors and multiple b cell cancers
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8752722/
https://www.ncbi.nlm.nih.gov/pubmed/35017485
http://dx.doi.org/10.1038/s41467-021-27853-w
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