Targeted release of a bispecific fusion protein SIRPα/Siglec-10 by oncolytic adenovirus reinvigorates tumor-associated macrophages to improve therapeutic outcomes in solid tumors.

ABSTRACT:

Background

The pleiotropic roles of tumor-associated macrophages (TAMs) render them attractive targets in antitumor drug development. CD47/SIRPα (signal regulatory protein alpha) and CD24/Siglec-10 (sialic acid-binding immunoglobulin-like lectin 10) signaling pathways have been found to suppress macrophage phagocytosis of malignant cells. Systemic blockade of CD47/SIRPα has shown severe side effects. Intratumoral delivery of a CD47 inhibitor by oncolytic viruses (OVs) may circumvent this hurdle.

Methods

To identify the characteristics of recombinant adenovirus (AdV)-SIRPα/Siglec-10, we conducted CCK8 assay, quantitative PCR, western blot, competitive binding assay, in vitro cytotoxicity assay, ELISA and phagocytosis assay. We investigated the antitumor immune responses of Ad

SUBMITTER: Zhang Y 

PROVIDER: S-EPMC11962785 | biostudies-literature | 2025 Apr

REPOSITORIES: biostudies-literature