IMR Press / FBL / Volume 25 / Issue 9 / DOI: 10.2741/4877

Frontiers in Bioscience-Landmark (FBL) is published by IMR Press from Volume 26 Issue 5 (2021). Previous articles were published by another publisher on a subscription basis, and they are hosted by IMR Press on imrpress.com as a courtesy and upon agreement with Frontiers in Bioscience.

Open Access Article
PLAP -CAR T cells mediate high specific cytotoxicity against colon cancer cells
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1 Department of Hematology, The Third Xiangya Hospital, Central South University, Changsha 410013, PR China
2 Promab Biotechnologies, 2600 Hilltop Drive, Richmond, CA, 94806, USA
3 Biology and Environmental Science College, Hunan University of Arts and Science, Changde, 415000, China
4 Cancer and Immunogenetics Laboratory, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, Oxford, UK, OV3 9DS
Front. Biosci. (Landmark Ed) 2020, 25(9), 1765–1786; https://doi.org/10.2741/4877
Published: 1 June 2020
(This article belongs to the Special Issue FAK signaling)
Abstract

Placental alkaline phosphatase, PLAP encoded by ALPP gene in humans is mainly expressed in placenta and testis, and not expressed in any other normal tissues. PLAP is overexpressed in colorectal cancers which makes it an attractive target for CAR (chimeric antigen receptor)-T cell therapy. PLAP mRNA expression was detected in 21.5% (25 out of 116) of colorectal cancer cell lines and this expression was confirmed by FACS at the protein level. In addition, IHC staining on primary colorectal cancer tumors demonstrated PLAP expression in >20% of colorectal cancer tumors. We generated mouse and humanized PLAP ScFv-CAR-T cells and demonstrated high specificity against PLAP-positive colon cancer cells using RTCA (real-time cytotoxicity assay) and IFN-gamma secretion. In addition, humanized-CAR-T cells significantly decreased Lovo xenograft tumor growth in vivo. The combination of hPLAP-CAR-T cells with PD-1, PD-L1 or LAG-3 checkpoint inhibitors significantly increased the activity of hPLAP-CAR-T cells. This study demonstrates ability of novel PLAP-CAR-T cells to kill colorectal cancers and that the extent of killing can be increased by combination with checkpoint inhibitors.

Keywords
Chimeric Antigen Receptor
Immunotherapy
Cancer
PLAP
Checkpoint inhibitor
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