TEM8/ANTXR1-Specific CAR T cells as a targeted therapy for triple-negative breast cancer

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 Zein-Eldin Powell, Matthew L. Baker, Winfried S. Wels, Joachim Koch, Poul H. Sorensen, Benjamin Deneen, Matthew J. EllisMichael T. Lewis, Meenakshi Hegde, Bradley S. Fletcher, Brad St Croix, Nabil Ahmed

Research output: Contribution to journalArticle

47 Scopus citations

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 TEM8þ 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.

Original languageEnglish (US)
Pages (from-to)489-500
Number of pages12
JournalCancer research
Volume78
Issue number2
DOIs
StatePublished - Jan 15 2018

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Fingerprint Dive into the research topics of 'TEM8/ANTXR1-Specific CAR T cells as a targeted therapy for triple-negative breast cancer'. Together they form a unique fingerprint.

Cite this