Targeted chain-exchange-mediated reconstitution of a split type-I cytokine for conditional immunotherapy.

ABSTRACT: Antibody-cytokine fusions targeted against tumor-associated antigens (TAAs) are promising cancer immunotherapy agents, with many such molecules currently undergoing clinical trials. However, due to the limited number of tumor-specific targets, on-target off-tumor effects can lead to systemic toxicity. Additionally, targeted cytokines can be scavenged by cytokine receptors on peripheral cells, decreasing tumor penetration. This study aims at overcoming these issues by engineering a platform for targeted conditionally active type I cytokines. Building on our previously reported PACE (Prodrug-Activating Chain Exchange) platform, we split the type I cytokine interleukin-4 (IL-4) to create two inactive IL-4 prodrugs, and fused these split IL-4 counterparts to the C-t

SUBMITTER: Vasic V 

PROVIDER: S-EPMC10448976 | biostudies-literature | 2023 Jan-Dec

REPOSITORIES: biostudies-literature