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.
Juheon Lee  #  1 ,  Jinhoo Song  #  1 ,  Wonbeak Yoo  2 ,  Hyunji Choi  2 ,  Dana Jung  1 ,  Eunjeong Choi  1 ,  Seo-Gyeong Jo  1 ,  Eun-Yeung Gong  3 ,  Young-Hee Jeoung  3 ,  You-Soo Park  4 ,  Woo-Chang Son  4 ,  Hosuk Lee  5 ,  Hayoung Lee  5 ,  Jeom Ji Kim  5 ,  TaeEun Kim  5 ,  Sooyun Lee  6 ,  Jang-June Park  7 ,  Tae-Don Kim  8  9 ,  Seok-Ho Kim  10  11
Affiliations
  • 1. Department of Health Sciences, The Graduate School of Dong-A University, Busan, 49315, Republic of Korea.
  • 2. Personalized Genomic Medicine Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon, 34141, Republic of Korea.
  • 3. Department of Medicinal Biotechnology, College of Health Science, Dong-A University, Busan, 49315, Republic of Korea.
  • 4. Department of Research Center, Dongnam Institute of Radiological and Medical Sciences Busan, Busan, 46033, Republic of Korea.
  • 5. ISU Abxis, Drug Discovery Division, Bundang-gu, Seongnam-si, Gyeonggi-do, 13488, Republic of Korea.
  • 6. Immunotherapy Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon, 34141, Republic of Korea.
  • 7. ISU Abxis, Drug Discovery Division, Bundang-gu, Seongnam-si, Gyeonggi-do, 13488, Republic of Korea. [email protected].
  • 8. Immunotherapy Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon, 34141, Republic of Korea. [email protected].
  • 9. Department of Functional Genomics, KRIBB School of Bioscience, Korea University of Science and Technology (UST), 217 Gajeong-ro, Yuseong-gu, Daejeon, 34113, Republic of Korea. [email protected].
  • 10. Department of Health Sciences, The Graduate School of Dong-A University, Busan, 49315, Republic of Korea. [email protected].
  • 11. Department of Medicinal Biotechnology, College of Health Science, Dong-A University, Busan, 49315, Republic of Korea. [email protected].
  • # Contributed equally.
PMID: 39751931 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.
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