alexa Evolution of Potent and Stable Placental-Growth-Factor-1-Targeting CovX-Bodies from Phage Display Peptide Discovery.


Immunotherapy: Open Access

Author(s): Bower KE, Lam SN, Oates BD, Del Rosario JR, Corner E

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Novel phage-derived peptides are the first reported molecules specifically targeting human placental growth factor 1 (PlGF-1). Phage data enabled peptide modifications that decreased IC(50) values in PlGF-1/VEGFR-1 competition ELISA from 100 to 1 μM. Peptides exhibiting enhanced potency were bioconjugated to the CovX antibody scaffold 1 (CVX-2000), generating bivalent CovX-Bodies with 2 nM K(D) against PlGF-1. In vitro and in vivo peptide cleavage mapping studies enabled the identification of proteolytic hotspots that were subsequently chemically modified. These changes decreased IC(50) to 0.4 nM and increased compound stability from 5% remaining at 6 h after injection to 35% remaining at 24 h with a β phase half-life of 75 h in mice. In cynomolgus monkey, a 78 h β half-life was observed for lead compound 2. The pharmacological properties of 2 are currently being explored. This article was published in Journal of Medicinal Chemistry and referenced in Immunotherapy: Open Access

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