@article{TEXTUAL, recid = {11035}, author = {Sasaki, Koichi and Ishihara, Jun and Ishihara, Ako and Miura, Risako and Mansurov, Aslan and Fukunaga, Kazuto and Hubbell, Jeffrey A.}, title = {Engineered collagen-binding serum albumin as a drug conjugate carrier for cancer therapy}, journal = {Science Advances}, address = {2019-08-14}, number = {TEXTUAL}, 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.}, url = {http://knowledge.uchicago.edu/record/11035}, }