論文

国際誌
2019年8月

Engineered collagen-binding serum albumin as a drug conjugate carrier for cancer therapy.

Science advances
  • Koichi Sasaki
  • ,
  • Jun Ishihara
  • ,
  • Ako Ishihara
  • ,
  • Risako Miura
  • ,
  • Aslan Mansurov
  • ,
  • Kazuto Fukunaga
  • ,
  • Jeffrey A Hubbell

5
8
開始ページ
eaaw6081
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.aaw6081

Serum albumin (SA) is used as a carrier to deliver cytotoxic agents to tumors via passive targeting. To further improve SA's tumor targeting capacity, we sought to develop an approach to retain SA-drug conjugates within tumors through a combination of passive and active targeting. SA was recombinantly fused with a collagen-binding domain (CBD) of von Willebrand factor to bind within the tumor stroma after extravasation due to tumor vascular permeability. Doxorubicin (Dox) was conjugated to the CBD-SA via a pH-sensitive linker. Dox-CBD-SA treatment significantly suppressed tumor growth compared to both Dox-SA and aldoxorubicin treatment in a mouse model of breast cancer. Dox-CBD-SA efficiently stimulated host antitumor immunity, resulting in the complete eradication of MC38 colon carcinoma when used in combination with anti-PD-1 checkpoint inhibitor. Dox-CBD-SA decreased adverse events compared to aldoxorubicin. Thus, engineered CBD-SA could be a versatile and clinically relevant drug conjugate carrier protein for treatment of solid tumors.

リンク情報
DOI
https://doi.org/10.1126/sciadv.aaw6081
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/31453327
PubMed Central
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6693903
ID情報
  • DOI : 10.1126/sciadv.aaw6081
  • PubMed ID : 31453327
  • PubMed Central 記事ID : PMC6693903

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