TEM8/ANTXR1-Specific CAR T Cells as a Targeted Therapy for Triple-Negative Breast Cancer.
Cancer Res
; 78(2): 489-500, 2018 01 15.
Article
in En
| MEDLINE
| ID: mdl-29183891
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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Receptors, Antigen, T-Cell
/
T-Lymphocytes
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Receptors, Cell Surface
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Triple Negative Breast Neoplasms
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Cell- and Tissue-Based Therapy
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Immunotherapy
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Lung Neoplasms
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Neoplasm Proteins
Type of study:
Observational_studies
/
Prognostic_studies
/
Risk_factors_studies
Limits:
Animals
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Female
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Humans
Language:
En
Journal:
Cancer Res
Year:
2018
Document type:
Article