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

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

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. jangjune.park@isu.co.kr.
  • 8 Immunotherapy Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon, 34141, Republic of Korea. tdkim@kribb.re.kr.
  • 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. tdkim@kribb.re.kr.
  • 10 Department of Health Sciences, The Graduate School of Dong-A University, Busan, 49315, Republic of Korea. cvaccine@dau.ac.kr.
  • 11 Department of Medicinal Biotechnology, College of Health Science, Dong-A University, Busan, 49315, Republic of Korea. cvaccine@dau.ac.kr.
  • # 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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