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

Laura Codarri Deak; Masao Hashimoto; Pablo Umaña; Christian Klein

doi:10.1080/2162402X.2023.2197360

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

Oncoimmunology. 2023 Mar 30;12(1):2197360. doi: 10.1080/2162402X.2023.2197360. eCollection 2023.

Authors

Laura Codarri Deak¹, Masao Hashimoto², Pablo Umaña¹, Christian Klein¹

Affiliations

¹ Roche Innovation Center Zurich, Cancer Immunotherapy Discovery, Roche Pharma Research and Early Development, Schlieren, Switzerland.
² Emory Vaccine Center and Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, GA, USA.

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.

Keywords: Eciskafusp alfa; IL-2; PD-1; PD1-IL2v; RG6279; TCF-1.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Arenaviridae Infections
CD8-Positive T-Lymphocytes* / immunology
Cell Differentiation
Cytokines* / pharmacology
Humans
Immune Checkpoint Inhibitors* / pharmacology
Immunotherapy
Lymphocytic choriomeningitis virus
Mice
Mice, Inbred C57BL
Programmed Cell Death 1 Receptor* / antagonists & inhibitors
Receptors, Interleukin-2

Substances

Cytokines
Immune Checkpoint Inhibitors
PDCD1 protein, human
Receptors, Interleukin-2
Programmed Cell Death 1 Receptor

Grants and funding

Part of the work by MH was co-funded by Roche.