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

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

  2. Author Address

    Baylor Coll Med, Dept Translat Biol & Mol Med, Houston, TX 77030 USA.Texas Childrens Hosp, Baylor Coll Med, Houston Methodist Hosp, Ctr Cell & Gene Therapy, Houston, TX 77030 USA.Texas Childrens Hosp, Texas Childrens Canc Ctr, Houston, TX 77030 USA.NCI, Ctr Canc Res, Frederick, MD 21701 USA.Childrens Canc Hosp Egypt, CCHE 57357, El Saida Zenab, Cairo Governora, Egypt.Baylor Coll Med, Lester & Sue Smith Breast Ctr, Houston, TX 77030 USA.Univ British Columbia, Dept Urol Sci, Vancouver, BC, Canada.Vancouver Prostate Ctr, Vancouver, BC, Canada.Texas Childrens Hosp, Dept Pediat Pathol, Houston, TX 77030 USA.Houston Methodist Hosp, Dept Pathol Anat, Houston, TX USA.Baylor Coll Med, Dept Biochem & Mol Biol, Houston, TX 77030 USA.Inst Tumor Biol & Expt Therapy, Georg Speyer Haus,Paul Ehrlich Str, Frankfurt, Germany.Johannes Gutenberg Univ Mainz, Med Ctr, Inst Med Microbiol & Hyg, Mainz, Germany.British Columbia Canc Res Ctr, Dept Mol Oncol, Vancouver, BC, Canada.Univ British Columbia, Dept Pathol & Lab Med, Vancouver, BC, Canada.Baylor Coll Med, Dept Neurosci, Houston, TX 77030 USA.Univ Florida, Dept Med, Gainesville, FL USA.
    1. Year: 2018
    2. Date: JAN 15
  2. Journal: CANCER RESEARCH
  3. AMER ASSOC CANCER RESEARCH,
    1. 78
    2. 2
    3. Pages: 489-500
  5. Type of Article: Article
  6. ISSN: 0008-5472
  1. 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 mammo-spheres 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.

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External Sources

  1. View Full Text
  2. DOI: 10.1158/0008-5472.CAN-16-1911
  3. PMID: 29183891
  4. PMCID: PMC5771806
  5. View record in Web of Science®
  6. WOS: 000422875400016

Library Notes

  1. Fiscal Year: FY2017-2018
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