Oncolytic Newcastle-disease-virus-mediated CD47 blockade in preclinical melanoma and pancreatic cancer models.

ABSTRACT: Newcastle disease virus (NDV) exhibits strong immunostimulatory activity and a favorable safety profile, but its moderate monotherapy efficacy may be improved through combination therapies. Although NDV selectively infects and lyses tumor cells, viral infection unintentionally elevates tumor-cell CD47 expression-a "don't-eat-me" signal that could mask the full immunostimulatory potential of NDV. To offset this adverse host response, we engineered NDVs that expressed an anti-CD47 antibody or SIRPα-Fc immunoadhesin to pair direct oncolysis with local CD47 blockade to amplify SIRPα⁺ phagocytic-cell-mediated clearance of tumor cells and downstream antitumor immunity, as well as circumvent dose-related toxicities associated with systemic administration of CD47-blocking agents. NDV-me

SUBMITTER: Yates JGE 

PROVIDER: S-EPMC12657332 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature