BioCentury
ARTICLE | Distillery Therapeutics

Tumor-targeted serum albumin-chemotherapy conjugates for improved delivery to breast and colorectal cancers

September 12, 2019 9:10 PM UTC

INDICATION: Breast cancer; colorectal cancer

Delivering chemotherapies through conjugation to tumor-targeted albumin could treat breast and colorectal cancers. Albumin is fused with collagen-binding domain of vWF to facilitate attachment to the tumor stroma, and subsequently conjugated to chemotherapy drugs via a linker that is cleaved in acidic environments like the tumor microenvironment. In vitro, a drug-free vWF-albumin fusion bound COL1 and COL3 with Kd values of 1.8 and 40.6 nM, respectively. Fusions conjugated to aldoxorubicin increased intratumoral accumulation of doxorubicin compared with free drug and reduced tumor volume, extended survival and led to complete tumor remission in 17% of mice with breast cancer. In a mouse model of colorectal cancer, the aldoxorubicin conjugates plus a mAb against PD-1 eradicated established tumors, prolonged lifespan and induced resistance to tumor rechallenge...