Abstract 2312: TEM8/ANTXR1 specific T cells co-target tumor stem cells and tumor vasculature in triple-negative breast cancer

Abstract

Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer with no approved targeted therapies. Tumor endothelial marker 8 (TEM8), initially identified as a marker of tumor endothelial cells in colorectal cancer and other solid tumors has recently been shown to be upregulated in TNBC and breast cancer stem cells (BCSCs). We investigated whether TEM8 specific chimeric antigen receptor (CAR) T cells recognize and kill both tumor endothelial cells as well as TNBC tumor cells. TEM8 specific CAR molecules were generated using single chain variable fragment derived from the monoclonal antibody, L2. L2 CAR T cells selectively recognized TEM8, secreted immunostimulatory cytokines and effectively killed both TEM8 positive TNBC and tumor endothelial cell lines. Moreover, L2 CAR T cells targeted breast cancer stem cells significantly reducing the number of mammospheres relative to non-transduced T cells. In vivo, adoptive transfer of L2 CAR T cells induced regression of established vascularized TNBC xenografts. Hence, TEM8 may serve as an attractive target for immunotherapy of TNBC. Citation Format: Tiara Byrd, Kristen Fousek, Antonella Pignata, Christopher Szot, Kevin Bielamowicz, Steven Seaman, Daniel Landi, Nino Rainusso, Poul Sorensen, Joachim Koch, Winfried Wels, Bradley Fletcher, Meenakshi Hegde, Brad St Croix, Nabil Ahmed. TEM8/ANTXR1 specific T cells co-target tumor stem cells and tumor vasculature in triple-negative breast cancer. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 2312.

AlInhibition mechanism of PinX1 Gene on cancer stem cells of nasopharyngeal carcinoma

“…Therefore, tumor stem cells are the main cause of cancer. Eliminating tumor stem cells means eliminating tumors (24,25).…”

Seneca Valley Virus Exploits TEM8, a Collagen Receptor Implicated in Tumor Growth

“…TEM8, a ~85 kDa cell surface transmembrane glycoprotein, was originally identified based on its elevated expression in colorectal tumor endothelium ( 5 ). Subsequently, TEM8 was found to be elevated in other tumor-associated cell types, including cancer-associated fibroblasts, pericytes and occasionally tumor cells themselves ( 5 , 9 , 11 , 18 , 25 ). Although TEM8 was the first identified PA receptor, a second cellular receptor, CMG2, was discovered shortly thereafter in endothelial cells, and shares a similar structure to TEM8 ( 21 , 26 , 27 ).…”

“…TEM8 itself has been previously proposed as a target for cancer therapy using monoclonal antibodies, drug-conjugated antibodies, and vaccines ( 9 , 11 , 16 , 17 ). TEM8 may also function as a biomarker for different tumors types including, among others, lung, breast, and colorectal cancer ( 9 , 11 , 18 – 20 ).…”