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<p>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.</p>

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

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年1月3日

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  • Juheon Lee,
  • Jinhoo Song,
  • Wonbeak Yoo,
  • Hyunji Choi,
  • Dana Jung,
  • Eunjeong Choi,
  • Seo-Gyeong Jo,
  • Eun-Yeung Gong,
  • Young-Hee Jeoung,
  • You-Soo Park,
  • Woo-Chang Son,
  • Hosuk Lee,
  • Hayoung Lee,
  • Jeom Ji Kim,
  • TaeEun Kim,
  • Sooyun Lee,
  • Jang-June Park,
  • Tae-Don Kim,
  • Seok-Ho Kim

摘要

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.