Beyond checkpoint inhibition: PD-1 cis-targeting of an IL-2R beta gamma-biased interleukin-2 variant as a novel approach to build on checkpoint inhibition

• Type of Material: Article
• Authors: Laura C Deak, Roche Pharma Research and Early Development; Masao Hashimoto, Emory University; Pablo Umana, Roche Pharma Research and Early Development; Christian Klein, Roche Pharma Research and Early Development
• Language: English
• Date: 2023-12-31
• Publisher: TAYLOR & FRANCIS INC
• Publication Version: Final Published Version
• Copyright Statement: © 2023 The Author(s). Published with license by Taylor & Francis Group, LLC.
• License: Creative Commons Attribution-NonCommercial 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1080/2162402X.2023.2197360
• Title of Journal or Parent Work: ONCOIMMUNOLOGY
• Volume: 12
• Issue: 1
• Start Page: 2197360
• End Page: 2197360
• Grant/Funding Information: Part of the work by MH was co-funded by Roche.
• Keywords: Life Sciences & Biomedicine; Oncology; PD1-IL2v; CYTOKINE; Immunology; Science & Technology; IL-2; RG6279; Eciskafusp alfa; PD-1; TCF-1
• Research Categories: Health Sciences, Immunology; Biology, Microbiology

Abstract

The immunocytokine PD1-IL2v was designed to overcome liabilities and improve efficacy of IL-2 therapies. PD1-IL2v preferentially targets PD-1+ T-cells and acts on antigen-specific stem-like PD-1+ TCF-1+ CD8+ T-cells expanding and differentiating them towards better effectors resulting in superior efficacy in LCMV chronic infection and tumor models compared to checkpoint inhibition.