CAR T-cell therapy for triple-negative breast cancer: Where we are

Cancer Lett. 2020 Oct 28:491:121-131. doi: 10.1016/j.canlet.2020.07.044. Epub 2020 Aug 12.

Abstract

Triple-negative breast cancer (TNBC) is the most complex and challenging breast cancer subtype to treat, and chemotherapy remains the standard of care. Clinically, TNBC has a relatively high rate of recurrence and poor prognosis, which leads to a significant effort to discover novel strategies to treat patients with these tumors. Currently, chimeric antigen receptor (CAR) T cell-based immunotherapy redirects the patient's immune system directly to recognize and eradicate tumor-associated antigens (TAAs) expressing tumor cells being explored as a treatment for TNBC. A steadily increasing research in CAR T-cell therapy targeting different TAAs in TNBC has reported. In this review, we introduce the CAR technology and summarize the potential TAAs, available CARs, the antitumor activity, and the related toxicity of CARs currently under investigation for TNBC. We also highlight the potential strategies to prevent/reduce potential "on target, off tumor" toxicity induced by CAR T-cell therapy. This review will help to explore proper targets to expand further the CAR T-cell therapy for TNBCs in the clinic.

Keywords: Chimeric antigen receptor; Immunotherapy; T cells; Triple-negative breast cancer; Tumor antigens.

Publication types

  • Review

MeSH terms

  • Antigens, Neoplasm / immunology
  • Chondroitin Sulfate Proteoglycans / immunology
  • Female
  • Folate Receptor 1 / immunology
  • GPI-Linked Proteins / immunology
  • Humans
  • Immunotherapy, Adoptive / adverse effects
  • Immunotherapy, Adoptive / methods*
  • Intercellular Adhesion Molecule-1 / immunology
  • Membrane Proteins / immunology
  • Mesothelin
  • Mucin-1 / immunology
  • NK Cell Lectin-Like Receptor Subfamily K / immunology
  • Receptor Tyrosine Kinase-like Orphan Receptors / immunology
  • Triple Negative Breast Neoplasms / therapy*

Substances

  • Antigens, Neoplasm
  • CSPG4 protein, human
  • Chondroitin Sulfate Proteoglycans
  • Folate Receptor 1
  • GPI-Linked Proteins
  • KLRK1 protein, human
  • MUC1 protein, human
  • Membrane Proteins
  • Mucin-1
  • NK Cell Lectin-Like Receptor Subfamily K
  • Intercellular Adhesion Molecule-1
  • ROR1 protein, human
  • Receptor Tyrosine Kinase-like Orphan Receptors
  • Mesothelin