Therapeutic potential of anti-ErbB3 chimeric antigen receptor natural killer cells against breast cancer

Cancer Immunol Immunother. 2025 Jan 3;74(2):73. doi: 10.1007/s00262-024-03923-y.

Abstract

ErbB3 is markedly overexpressed in breast cancer cells and is associated with resistance and metastasis. Additionally, ErbB3 expression levels are positively correlated with low densities of tumor-infiltrating lymphocytes, a marker of poor prognosis. Consequently, ErbB3 is a promising therapeutic target for cancer immunotherapy. Here, we report the generation of ErbB3-targeted chimeric antigen receptor (CAR)-modified natural killer (NK) cells by transducing cord blood-derived primary NK cells using vsv-g envelope-pseudotyped lentiviral vectors. Transduced cells displayed stable CAR-expressing activity and increased cytotoxicity against ErbB3-positive breast cancer cell lines. Furthermore, anti-ErbB3 (aErbB3) CAR-NK cells strongly reduced the tumor burden in the SK-BR-3 xenograft mouse model without observable side effects. These findings underscore the potential of aErbB3 CAR-NK cells as targeted immunotherapy for ErbB3-positive breast cancer, suggesting a promising alternative to conventional treatments.

Keywords: Breast cancer; Chimeric antigen receptor (CAR); ErbB3; Natural killer (NK) cells.

MeSH terms

  • Animals
  • Breast Neoplasms* / immunology
  • Breast Neoplasms* / therapy
  • Cell Line, Tumor
  • Female
  • Humans
  • Immunotherapy, Adoptive / methods
  • Killer Cells, Natural* / immunology
  • Killer Cells, Natural* / transplantation
  • Mice
  • Mice, SCID
  • Receptor, ErbB-3* / immunology
  • Receptor, ErbB-3* / metabolism
  • Receptors, Chimeric Antigen* / genetics
  • Receptors, Chimeric Antigen* / immunology
  • Xenograft Model Antitumor Assays*

Substances

  • Receptors, Chimeric Antigen
  • Receptor, ErbB-3
  • ERBB3 protein, human