Universal Fab-Fc masked cytokine prodrug platform: αPD-L1/IL-15 prodrug activates CD44⁺ CD8⁺ T cells in tumor-draining lymph nodes to enhance antitumor immunity.

ABSTRACT:

Background

Immunocytokines targeting immune checkpoints have shown great potential in overcoming resistance to immune checkpoint blockade (ICB), making them a major focus of development in recent years. However, severe dose-limiting toxicity hindered their clinical application. Therefore, it is vital to develop versatile strategies to improve safety and elucidate the underlying mechanisms of resistance reversal for advancing immunocytokine therapy.

Methods

A general prodrug platform was established to construct interleukin (IL)-15 and IL-12-based immunocytokine prodrugs (P-T, P-Y, and P-Y-IL12). The efficacy of the masking strategy was validated by in vitro activity assays and in vivo safety evaluations. Antitumor efficacy of P-T was assessed in two murine cold tumor models.

SUBMITTER: Song L 

PROVIDER: S-EPMC12314929 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature