Abstract 4228: PLAP (placental alkaline phosphatase)-CAR-T cells specifically target colorectal cancer

Abstract

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 a proportion of colorectal cancers which makes it an attractive target for CAR (chimeric antigen receptor)-T cell therapy. PLAP mRNA expression was detected in 21.4% (25 out of 117) 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, PDL-1 or LAG-3 checkpoint inhibitors significantly increased the activity of hPLAP-CAR-T cells. Significance: 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. These preclinical results suggest that PLAP-CAR-T cells combined with checkpoint inhibitors may be developed into an effective clinical therapy for PLAP expressing colorectal and other cancers. Citation Format: Vita M. Golubovskaya, Robert Berahovich, Hua Zhou, Xianghong Liu, Feng Li, Shirley Xu, Yuehua Wei, Djamila Ouaret, Walter Bodmer, Lijun Wu. PLAP (placental alkaline phosphatase)-CAR-T cells specifically target colorectal cancer [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 4228.