Novel CS1 CAR-T Cells and Bispecific CS1-BCMA CAR-T Cells Effectively Target Multiple Myeloma

Multiple myeloma (MM) is a hematological cancer caused by abnormal proliferation of plasma cells in the bone marrow, and novel types of treatment are needed for this deadly disease. In this study, we aimed to develop novel CS1 CAR-T cells and bispecific CS1-BCMA CAR-T cells to specifically target mu...

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Autores principales: Golubovskaya, Vita, Zhou, Hua, Li, Feng, Berahovich, Robert, Sun, Jinying, Valentine, Michael, Xu, Shirley, Harto, Hizkia, Sienkiewicz, John, Huang, Yanwei, Wu, Lijun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8533376/
https://www.ncbi.nlm.nih.gov/pubmed/34680541
http://dx.doi.org/10.3390/biomedicines9101422
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author Golubovskaya, Vita
Zhou, Hua
Li, Feng
Berahovich, Robert
Sun, Jinying
Valentine, Michael
Xu, Shirley
Harto, Hizkia
Sienkiewicz, John
Huang, Yanwei
Wu, Lijun
author_facet Golubovskaya, Vita
Zhou, Hua
Li, Feng
Berahovich, Robert
Sun, Jinying
Valentine, Michael
Xu, Shirley
Harto, Hizkia
Sienkiewicz, John
Huang, Yanwei
Wu, Lijun
author_sort Golubovskaya, Vita
collection PubMed
description Multiple myeloma (MM) is a hematological cancer caused by abnormal proliferation of plasma cells in the bone marrow, and novel types of treatment are needed for this deadly disease. In this study, we aimed to develop novel CS1 CAR-T cells and bispecific CS1-BCMA CAR-T cells to specifically target multiple myeloma. We generated a new CS1 (CD319, SLAM-7) antibody, clone (7A8D5), which specifically recognized the CS1 antigen, and we applied it for the generation of CS1-CAR. CS1-CAR-T cells caused specific killing of CHO-CS1 target cells with secretion of IFN-gamma and targeted multiple myeloma cells. In addition, bispecific CS1-BCMA-41BB-CD3 CAR-T cells effectively killed CHO-CS1 and CHO-BCMA target cells, killed CS1/BCMA-positive multiple myeloma cells, and secreted IFN-gamma. Moreover, CS1-CAR-T cells and bispecific CS1-BCMA CAR-T cells effectively blocked MM1S multiple myeloma tumor growth in vivo. These data for the first time demonstrate that novel CS1 and bispecific CS1-BCMA-CAR-T cells are effective in targeting MM cells and provide a basis for future clinical trials.
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spelling pubmed-85333762021-10-23 Novel CS1 CAR-T Cells and Bispecific CS1-BCMA CAR-T Cells Effectively Target Multiple Myeloma Golubovskaya, Vita Zhou, Hua Li, Feng Berahovich, Robert Sun, Jinying Valentine, Michael Xu, Shirley Harto, Hizkia Sienkiewicz, John Huang, Yanwei Wu, Lijun Biomedicines Article Multiple myeloma (MM) is a hematological cancer caused by abnormal proliferation of plasma cells in the bone marrow, and novel types of treatment are needed for this deadly disease. In this study, we aimed to develop novel CS1 CAR-T cells and bispecific CS1-BCMA CAR-T cells to specifically target multiple myeloma. We generated a new CS1 (CD319, SLAM-7) antibody, clone (7A8D5), which specifically recognized the CS1 antigen, and we applied it for the generation of CS1-CAR. CS1-CAR-T cells caused specific killing of CHO-CS1 target cells with secretion of IFN-gamma and targeted multiple myeloma cells. In addition, bispecific CS1-BCMA-41BB-CD3 CAR-T cells effectively killed CHO-CS1 and CHO-BCMA target cells, killed CS1/BCMA-positive multiple myeloma cells, and secreted IFN-gamma. Moreover, CS1-CAR-T cells and bispecific CS1-BCMA CAR-T cells effectively blocked MM1S multiple myeloma tumor growth in vivo. These data for the first time demonstrate that novel CS1 and bispecific CS1-BCMA-CAR-T cells are effective in targeting MM cells and provide a basis for future clinical trials. MDPI 2021-10-09 /pmc/articles/PMC8533376/ /pubmed/34680541 http://dx.doi.org/10.3390/biomedicines9101422 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Golubovskaya, Vita
Zhou, Hua
Li, Feng
Berahovich, Robert
Sun, Jinying
Valentine, Michael
Xu, Shirley
Harto, Hizkia
Sienkiewicz, John
Huang, Yanwei
Wu, Lijun
Novel CS1 CAR-T Cells and Bispecific CS1-BCMA CAR-T Cells Effectively Target Multiple Myeloma
title Novel CS1 CAR-T Cells and Bispecific CS1-BCMA CAR-T Cells Effectively Target Multiple Myeloma
title_full Novel CS1 CAR-T Cells and Bispecific CS1-BCMA CAR-T Cells Effectively Target Multiple Myeloma
title_fullStr Novel CS1 CAR-T Cells and Bispecific CS1-BCMA CAR-T Cells Effectively Target Multiple Myeloma
title_full_unstemmed Novel CS1 CAR-T Cells and Bispecific CS1-BCMA CAR-T Cells Effectively Target Multiple Myeloma
title_short Novel CS1 CAR-T Cells and Bispecific CS1-BCMA CAR-T Cells Effectively Target Multiple Myeloma
title_sort novel cs1 car-t cells and bispecific cs1-bcma car-t cells effectively target multiple myeloma
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8533376/
https://www.ncbi.nlm.nih.gov/pubmed/34680541
http://dx.doi.org/10.3390/biomedicines9101422
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