@article{fa7cef93ae704b8b8e804fc3bc08945c,
title = "TEM8/ANTXR1-Specific CAR T cells as a targeted therapy for triple-negative breast cancer",
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{\th} TNBC tumor cells and targeting the tumor endothelium to block tumor neovascular-ization. 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.",
author = "Byrd, {Tiara T.} and Kristen Fousek and Antonella Pignata and Christopher Szot and Heba Samaha and Steven Seaman and Lacey Dobrolecki and Salsman, {Vita S.} and Oo, {Htoo Zarni} and Kevin Bielamowicz and Daniel Landi and Nino Rainusso and John Hicks and Powell, {Suzanne Zein-Eldin} and Baker, {Matthew L.} and Wels, {Winfried S.} and Joachim Koch and Sorensen, {Poul H.} and Benjamin Deneen and Ellis, {Matthew J.} and Lewis, {Michael T.} and Meenakshi Hegde and Fletcher, {Bradley S.} and Croix, {Brad St} and Nabil Ahmed",
note = "Funding Information: This research was supported in part by the Stand Up To Cancer - St. Baldrick's Pediatric Dream Team Translational Research Grant (SU2C-AACR-DT1113). Stand Up To Cancer is a program of the Entertainment Industry Foundation. Research grants are administered by the American Association for Cancer Research, the Scientific Partner of SU2C. Authors directly supported by this grant include N. Ahmed and M. Hegde. This research was also funded by the following T32 training grants: award numbers T32GM088129 and 5T32HL092332 from the National Institute of General Medical Sciences and National Heart, Lung and Blood Institute, respectively. The authors directly supported by both T32 grants include T. Byrd and K. Fousek. The Cytometry and Cell Sorting Core at Baylor College of Medicine also supported this project with funding from the NIH (AI036211 and CA125123). Publisher Copyright: {\textcopyright} 2017 American Association for Cancer Research.",
year = "2018",
month = jan,
day = "15",
doi = "10.1158/0008-5472.CAN-16-1911",
language = "English (US)",
volume = "78",
pages = "489--500",
journal = "Cancer research",
issn = "0008-5472",
publisher = "American Association for Cancer Research Inc.",
number = "2",
}