Retargeted adenoviruses for local IgA and CD47 blocker production as a novel cancer therapy

ABSTRACT: Despite advances in IgG-based cancer immunotherapy, challenges remain in effectively engaging innate immune responses against solid tumors. Here, IgA antibodies hold promise due to their ability to activate neutrophils and macrophages. We present a novel retargeted adenovirus-mediated approach that transforms cancer cells into "biofactories" for localized production of monomeric or dimeric IgA antibodies and a CD47 blocker to potentiate the effect of IgA antibodies. With our approach tumor cells effectively produced IgA antibodies against tumor antigens such as EGFR or EpCAM and a soluble SIRPα-Fc fusion protein, which blocks the CD47-SIRPα axis. In a perfused tumor-on-a-chip model, locally produced IgA triggered neutrophil- and macrophage-mediated tumor cell killing, further potentiated b

SUBMITTER: Mariya Chernyavska 

PROVIDER: S-SCDT-10_1038-S44321-026-00477-7 | biostudies-other |

REPOSITORIES: biostudies-other