論文

国際誌
2019年12月

Recruitment of CD103+ dendritic cells via tumor-targeted chemokine delivery enhances efficacy of checkpoint inhibitor immunotherapy.

Science advances
  • John-Michael Williford
  • ,
  • Jun Ishihara
  • ,
  • Ako Ishihara
  • ,
  • Aslan Mansurov
  • ,
  • Peyman Hosseinchi
  • ,
  • Tiffany M Marchell
  • ,
  • Lambert Potin
  • ,
  • Melody A Swartz
  • ,
  • Jeffrey A Hubbell

5
12
開始ページ
eaay1357
終了ページ
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1126/sciadv.aay1357

Although a clinical breakthrough for cancer treatment, it remains that a minority of patients respond to checkpoint inhibitor (CPI) immunotherapy. The composition of tumor-infiltrating immune cells has been identified as a key factor influencing CPI therapy success. Thus, enhancing tumor immune cell infiltration is a critical challenge. A lack of the chemokine CCL4 within the tumor microenvironment leads to the absence of CD103+ dendritic cells (DCs), a crucial cell population influencing CPI responsiveness. Here, we use a tumor stroma-targeting approach to deliver CCL4; by generating a fusion protein of CCL4 and the collagen-binding domain (CBD) of von Willebrand factor, we show that CBD fusion enhances CCL4 tumor localization. Intravenous CBD-CCL4 administration recruits CD103+ DCs and CD8+ T cells and improves the antitumor effect of CPI immunotherapy in multiple tumor models, including poor responders to CPI. Thus, CBD-CCL4 holds clinical translational potential by enhancing efficacy of CPI immunotherapy.

リンク情報
DOI
https://doi.org/10.1126/sciadv.aay1357
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/31844672
PubMed Central
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6905870
ID情報
  • DOI : 10.1126/sciadv.aay1357
  • PubMed ID : 31844672
  • PubMed Central 記事ID : PMC6905870

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