Development of Novel PD1/PD-L1 Antagonists Using Circular Cys-Knotted Micro Proteins
Abstract
During these two years we have also accomplished the design and expression of a FRET-based reporter to screen antagonists for the PD-1/PD-L1 complex. We have constructed and screened genetically-encoded libraries using the loops1 and 6 of cyclotide MCoTI-I. This library was screened and a bioactive cyclotide, MCo-101B, was selected. This cyclotide was able to inhibit the PD-1/PD-L1 with an IC50 value of 0.66 micronM. This exciting finding represents the first cyclotide selected by molecular evolution that can inhibit the PD-1/PD-L1 complex with sub-micronM activity. This cyclotide has been used to perform preliminary toxicology studies, not showing toxicity in mice with dosing up 10 mg/kg. The cyclotide is being tested for efficacy in vivo in a lung cancer syngeneic model in mice.
Document Details
- Document Type
- Technical Report
- Publication Date
- Sep 01, 2019
- Accession Number
- AD1093338
Entities
People
- Julio A Camarero
Organizations
- University of Southern California