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Figure S4 from TEM8/ANTXR1-Specific CAR T Cells as a Targeted Therapy for Triple-Negative Breast Cancer

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posted on 2023-03-31, 01:27 authored by Tiara T. Byrd, Kristen Fousek, Antonella Pignata, Christopher Szot, Heba Samaha, Steven Seaman, Lacey Dobrolecki, Vita S. Salsman, Htoo Zarni Oo, Kevin Bielamowicz, Daniel Landi, Nino Rainusso, John Hicks, Suzanne Powell, Matthew L. Baker, Winfried S. Wels, Joachim Koch, Poul H. Sorensen, Benjamin Deneen, Matthew J. Ellis, Michael T. Lewis, Meenakshi Hegde, Bradley S. Fletcher, Brad St. Croix, Nabil Ahmed

L2 CAR T cells provide a survival advantage and disrupt vessels and tumor architecture in TNBC xenografts .

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St. Baldrick's Pediatric Dream Team Translational Research

American Association for Cancer Research

National Institute of General Medical Sciences

NIH

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ARTICLE ABSTRACT

Triple-negative breast cancer (TNBC) is an aggressive disease lacking targeted therapy. In this study, we developed a CAR T cell–based immunotherapeutic strategy to target TEM8, a marker initially defined on endothelial cells in colon tumors that was discovered recently to be upregulated in TNBC. CAR T cells were developed that upon specific recognition of TEM8 secreted immunostimulatory cytokines and killed tumor endothelial cells as well as TEM8-positive TNBC cells. Notably, the TEM8 CAR T cells targeted breast cancer stem–like cells, offsetting the formation of mammospheres relative to nontransduced T cells. Adoptive transfer of TEM8 CAR T cells induced regression of established, localized patient-derived xenograft tumors, as well as lung metastatic TNBC cell line–derived xenograft tumors, by both killing TEM8+ TNBC tumor cells and targeting the tumor endothelium to block tumor neovascularization. Our findings offer a preclinical proof of concept for immunotherapeutic targeting of TEM8 as a strategy to treat TNBC.Significance: These findings offer a preclinical proof of concept for immunotherapeutic targeting of an endothelial antigen that is overexpressed in triple-negative breast cancer and the associated tumor vasculature. Cancer Res; 78(2); 489–500. ©2017 AACR.

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