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Preclinical Activity of Embryonic Annexin A2-Specific Chimeric Antigen Receptor T Cells Against Ovarian Cancer

Chimeric antigen receptors (CARs) have found clinical success in B cell malignancies, but a dearth of potential targets limits their wider clinical application, especially in solid tumours. Here, we describe the development of an anti-annexin A2 CAR, CAR(2448), derived from an antibody found to have...

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Autores principales: Leong, Leonard, Tan, Heng Liang, Cua, Simeon, Yong, Kylie Su Mei, Chen, Qingfeng, Choo, Andre
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7013580/
https://www.ncbi.nlm.nih.gov/pubmed/31936170
http://dx.doi.org/10.3390/ijms21020381
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author Leong, Leonard
Tan, Heng Liang
Cua, Simeon
Yong, Kylie Su Mei
Chen, Qingfeng
Choo, Andre
author_facet Leong, Leonard
Tan, Heng Liang
Cua, Simeon
Yong, Kylie Su Mei
Chen, Qingfeng
Choo, Andre
author_sort Leong, Leonard
collection PubMed
description Chimeric antigen receptors (CARs) have found clinical success in B cell malignancies, but a dearth of potential targets limits their wider clinical application, especially in solid tumours. Here, we describe the development of an anti-annexin A2 CAR, CAR(2448), derived from an antibody found to have activity against epithelial ovarian cancer cell lines. The spacer length of CAR(2448) was optimised based on in vitro cytotoxic activity against ovarian cancer (OC) cell lines via a real-time cytotoxicity assay. The longer spacer CAR(2448)L T cells exhibit significant effector activity, inducing inflammatory cytokine release and cytotoxicity against OC cell lines. Furthermore, CAR(2448)L-BBz T cells induced enhanced survival in an in vivo OC xenograft model and reduced tumour volume by 76.6%. Our preclinical studies of CAR(2448) suggest its potential for the unmet need of novel strategies for the treatment of ovarian cancer.
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spelling pubmed-70135802020-03-09 Preclinical Activity of Embryonic Annexin A2-Specific Chimeric Antigen Receptor T Cells Against Ovarian Cancer Leong, Leonard Tan, Heng Liang Cua, Simeon Yong, Kylie Su Mei Chen, Qingfeng Choo, Andre Int J Mol Sci Article Chimeric antigen receptors (CARs) have found clinical success in B cell malignancies, but a dearth of potential targets limits their wider clinical application, especially in solid tumours. Here, we describe the development of an anti-annexin A2 CAR, CAR(2448), derived from an antibody found to have activity against epithelial ovarian cancer cell lines. The spacer length of CAR(2448) was optimised based on in vitro cytotoxic activity against ovarian cancer (OC) cell lines via a real-time cytotoxicity assay. The longer spacer CAR(2448)L T cells exhibit significant effector activity, inducing inflammatory cytokine release and cytotoxicity against OC cell lines. Furthermore, CAR(2448)L-BBz T cells induced enhanced survival in an in vivo OC xenograft model and reduced tumour volume by 76.6%. Our preclinical studies of CAR(2448) suggest its potential for the unmet need of novel strategies for the treatment of ovarian cancer. MDPI 2020-01-07 /pmc/articles/PMC7013580/ /pubmed/31936170 http://dx.doi.org/10.3390/ijms21020381 Text en © 2020 by the authors. 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 (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Leong, Leonard
Tan, Heng Liang
Cua, Simeon
Yong, Kylie Su Mei
Chen, Qingfeng
Choo, Andre
Preclinical Activity of Embryonic Annexin A2-Specific Chimeric Antigen Receptor T Cells Against Ovarian Cancer
title Preclinical Activity of Embryonic Annexin A2-Specific Chimeric Antigen Receptor T Cells Against Ovarian Cancer
title_full Preclinical Activity of Embryonic Annexin A2-Specific Chimeric Antigen Receptor T Cells Against Ovarian Cancer
title_fullStr Preclinical Activity of Embryonic Annexin A2-Specific Chimeric Antigen Receptor T Cells Against Ovarian Cancer
title_full_unstemmed Preclinical Activity of Embryonic Annexin A2-Specific Chimeric Antigen Receptor T Cells Against Ovarian Cancer
title_short Preclinical Activity of Embryonic Annexin A2-Specific Chimeric Antigen Receptor T Cells Against Ovarian Cancer
title_sort preclinical activity of embryonic annexin a2-specific chimeric antigen receptor t cells against ovarian cancer
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7013580/
https://www.ncbi.nlm.nih.gov/pubmed/31936170
http://dx.doi.org/10.3390/ijms21020381
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