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The Evolving Protein Engineering in the Design of Chimeric Antigen Receptor T Cells
Open AccessArticle

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

1
Bioprocessing Technology Institute (BTI), Agency for Science, Technology and Research (A*STAR), Singapore 138668, Singapore
2
NUS Graduate School for Integrative Sciences and Engineering (NGS), National University of Singapore, Singapore 119077, Singapore
3
Institute of Molecular and Cell Biology (IMCB), Agency for Science, Technology and Research (A*STAR), Singapore 138673, Singapore
4
Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117545, Singapore
5
Department of Biomedical Engineering, Faculty of Engineering, National University of Singapore (NUS), Singapore 117575, Singapore
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2020, 21(2), 381; https://doi.org/10.3390/ijms21020381
Received: 29 November 2019 / Revised: 30 December 2019 / Accepted: 6 January 2020 / Published: 7 January 2020
(This article belongs to the Special Issue CAR-T Cell Therapy)
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. View Full-Text
Keywords: CAR-T cells; Ovarian cancer; Annexin A2; Solid tumours CAR-T cells; Ovarian cancer; Annexin A2; Solid tumours
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MDPI and ACS Style

Leong, L.; Tan, H.L.; Cua, S.; Yong, K.S.M.; Chen, Q.; Choo, A. Preclinical Activity of Embryonic Annexin A2-Specific Chimeric Antigen Receptor T Cells Against Ovarian Cancer. Int. J. Mol. Sci. 2020, 21, 381. https://doi.org/10.3390/ijms21020381

AMA Style

Leong L, Tan HL, Cua S, Yong KSM, Chen Q, Choo A. Preclinical Activity of Embryonic Annexin A2-Specific Chimeric Antigen Receptor T Cells Against Ovarian Cancer. International Journal of Molecular Sciences. 2020; 21(2):381. https://doi.org/10.3390/ijms21020381

Chicago/Turabian Style

Leong, Leonard; Tan, Heng L.; Cua, Simeon; Yong, Kylie S.M.; Chen, Qingfeng; Choo, Andre. 2020. "Preclinical Activity of Embryonic Annexin A2-Specific Chimeric Antigen Receptor T Cells Against Ovarian Cancer" Int. J. Mol. Sci. 21, no. 2: 381. https://doi.org/10.3390/ijms21020381

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