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

  • Sci Adv. 2019 Aug 14;5(8):eaaw6081. doi: 10.1126/sciadv.aaw6081.
Koichi Sasaki  1 ,  Jun Ishihara  1 ,  Ako Ishihara  1 ,  Risako Miura  1 ,  Aslan Mansurov  1 ,  Kazuto Fukunaga  1 ,  Jeffrey A Hubbell  1
Affiliations
  • 1. Pritzker School of Molecular Engineering, University of Chicago, Chicago, IL 60637, USA.
PMID: 31453327 DOI: 10.1126/sciadv.aaw6081
Abstract

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.

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