Journal
MABS
Volume 9, Issue 8, Pages 1262-1269Publisher
TAYLOR & FRANCIS INC
DOI: 10.1080/19420862.2017.1305529
Keywords
DARPin (R); HGF; multi-specificity; pharmacokinetics; serum albumin; VEGF
Categories
Ask authors/readers for more resources
MP0250 is a multi-domain drug candidate currently being tested in clinical trials for the treatment of cancer. It comprises one anti-vascular endothelial growth factor-A (VEGF-A), one anti-hepatocyte growth factor (HGF), and two anti-human serum albumin (HSA) DARPin (R) domains within a single polypeptide chain. While there is first clinical validation of a single-domain DARPin (R) drug candidate, little is known about DARPin (R) drug candidates comprising multiple domains. Here, we show that MP0250 can be expressed at 15g/L in soluble form in E. coli high cell-density fermentation, it is stable in soluble/frozen formulation for 2years as assessed by reverse phase HPLC, it has picomolar potency in inhibiting VEGF-A and HGF in ELISA and cellular assays, and its domains are simultaneously active as shown by surface plasmon resonance. The inclusion of HSA-binding DARPin (R) domains leads to a favorable pharmacokinetic profile in mouse and cynomolgus monkey, with terminal half-lives of similar to 30 hours in mouse and similar to 5 days in cynomolgus monkey. MP0250 is thus a highly potent drug candidate that could be particularly useful in oncology. Beyond MP0250, the properties of MP0250 indicate that multi-domain DARPin (R) proteins can be valuable next-generation drug candidates.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available