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    CAR-T Cells Immunotherapy, A New Approach for the Treatment of Triple Negative Breast Cancer

  • Ava Resae,1,*
    1. Department of Basic Sciences, School of veterinary medicine, University of Semnan


  • Introduction: Triple-negative breast cancer (TNBC) is an aggressive disease that lacks targeted therapy. It is estrogen and progesterone receptor negative, lacks human epidermal growth factor 2 (HER2) gene, and is very aggressive. There are currently no treatments for TNBC. Immunotherapy with chimeric antigen receptor (CAR)-T cells is a novel immunotherapy approach and has been effective in treatment of some hematologic tumors. However, its efficacy on solid tumors is under research.
  • Methods: In this study, we reviewed CAR-T cell-based immunotherapeutic strategies for TNBC. We searched articles from 2016-2021 within Google scholar, PubMed and ScienceDirect with keywords Triple-negative breast cancer and CAR-T. Our exclusion criteria were review articles. Sixty-nine articles were found and sixty-one of them were removed after reading the title or abstract. Eight articles were selected for this review.
  • Results: Therapy with TEM8-specific, EGFR-specific, AXL, ICAM1-specific, MUC28z and NKG2D CAR-T cells successfully reduced tumor size in both murine and patient-derived TNBC cell lines and induced regression and stasis. These CAR-T cells were chosen based on protein expression within the tumor micro-environment. These CAR-T cells increased pro-inflammatory cytokines like IFN-γ, TNF-α and IL-2, enhanced T cell persistence and displayed potent cytotoxic capacity. However, according to results, CAR-T cells were still less effective in TNBC solid tumors than in hematological malignancies. In ROR1-specific CAR-T cells, therapeutic effects were impaired due to anti-inflammatory cytokines such as TGF-β in tumor environment. Combining ROR1-specific CAR-T cells with SD-208, a TGF-β blocker reduced the immunosuppressive effect.
  • Conclusion: These results demonstrate that immunotherapy with CAR-T cells can be a promising approach for TNBC treatment. CAR-T cell therapy is very challenging for solid tumors like TNBC due to the immunosuppressive microenvironment in the tumor site. Combining CAR-T cell therapy with other therapies or blocking anti-inflammatory cytokines may offer a better approach for CAR-T cell therapy for solid tumors.
  • Keywords: CAR-T, TNBC, Breast Cancer, Immunotherapy