Accession Number:

AD1087147

Title:

Development of Novel PD1/PD L1 Antagonists Using Circular Cys Knotted Micro Proteins

Descriptive Note:

Technical Report,15 May 2016,14 May 2019

Corporate Author:

University of Southern California Los Angeles United States

Personal Author(s):

Report Date:

2019-09-01

Pagination or Media Count:

18.0

Abstract:

During these two years we have also accomplished the design and expression of a FRET-based reporter to screen antagonists for the PD-1PD-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-1PD-L1 with an IC50 value of 0.66 micrometer. This exciting finding represents the first cyclotide selected by molecular evolution that can inhibit the PD-1PD-L1 complex with sub-micrometer activity. This cyclotide has been used to perform preliminary toxicology studies, not showing toxicity in mice with dosing up 10 mgkg. The cyclotide is being tested for efficacy in vivo in a lung cancer syngeneic model in mice.

Subject Categories:

  • Medicine and Medical Research

Distribution Statement:

APPROVED FOR PUBLIC RELEASE