Targeting tumor-infiltrating regulatory T cells: combining CD47 and PD-L1 inhibition via a novel aptamer-siRNA chimera.

ABSTRACT: Tumor-infiltrating regulatory T (Treg) cells contribute to immune evasion and are associated with poor prognosis in solid tumors. While CD47 blockade has demonstrated efficacy in hematologic malignancies, its application in solid tumors is hindered by the antigen sink effect and lack of tumor selectivity. Here, we report a rationally designed aptamer-siRNA chimera that selectively targets intratumoral Treg cells by exploiting their co-expression of PD-L1 and CD47 within the tumor microenvironment. The PD-L1 aptamer enables selective binding to PD-L1⁺ Treg cells and simultaneously inhibits PD-L1-mediated immune suppression. Conjugated CD47 siRNA silences CD47 expression, abrogating the "don't eat me" signal and facilitating phagocytic clearance. Mechanistically, this chimera efficiently dep

SUBMITTER: Zeng Y 

PROVIDER: S-EPMC12708450 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature