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Annexin A2-Specific Chimeric Antigen Receptor T Cells Against Ovarian Cancer

2020_08 Andre Thumbnail
From Left: Dr Andre Choo, Leonard Leong

Authors

Leonard Leong 1,2, Heng Liang Tan 1, Simeon Cua 1, Kylie Su Mei Yong 3, Qingfeng Chen 3,4 and Andre Choo 1,5

1 Bioprocessing Technology Institute, Agency for Science, Technology and Research (A*STAR), Singapore
2 NUS Graduate School for Integrative Sciences and Engineering (NGS), National University of Singapore, Singapore
3 Institute of Molecular and Cell Biology (IMCB), Agency for Science, Technology and Research (A*STAR), Singapore
4 Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore
5 Department of Biomedical Engineering, Faculty of Engineering, National University of Singapore (NUS), Singapore

Published in International Journal of Molecular Sciences 2020 21(2): 381 (Online Version)

 

Abstract

Chimeric antigen receptor (CAR) T cells are a relatively new type of cell and gene therapy that have proven effective in treating blood cancers. However, they have had comparatively limited success against solid tumours, in part due to the lack of targets available. Here, we describe the development of a new CAR against ovarian cancer, targeting annexin A2. This new CAR construct, CAR(2448), was engineered from an antibody raised using our lab’s antibody discovery platform.

Specific aspects of the CAR(2448) construct were optimised using benchtop techniques, that previously required animal models. The final CAR(2448) T cell construct exhibits potent killing activity against ovarian cancer cells. In addition, CAR(2448) T cells prolonged the survival of mice with ovarian tumours. Our preclinical data suggest CAR(2448)’s potential to address the unmet need of novel strategies for the treatment of ovarian cancer.