Targeting PD-1⁺ T cells with small-format immunocytokines enhances IL-12 antitumor activity.

ABSTRACT: Immunostimulatory cytokines and immune checkpoint inhibitors hold promise as cancer therapeutics; however, their use is often limited by reduced efficacy and significant toxicity. In this study, we developed small-format immunocytokines (ICKs) based on interleukin-12 (IL-12) and blocking nanobodies (Nbs) targeting mouse and human programmed cell death 1 (PD-1) and programmed cell death ligand 1 (PD-L1). Both PD-1- and PD-L1-targeted ICKs demonstrated similar in vitro performance, significantly increasing IL-12 tethering to immune cells and enhancing T cell cytotoxic activity compared with IL-12 alone. The antitumor efficacy of ICKs was evaluated by intratumoral delivery using self-amplifying RNA-based vectors or as recombinant proteins in mice. Despite effective PD-L1-mediated tumor anchor

SUBMITTER: Silva-Pilipich N 

PROVIDER: S-EPMC11764877 | biostudies-literature | 2025 Jan

REPOSITORIES: biostudies-literature