Therapeutically targeting type I interferon directly to XCR1+ dendritic cells reveals the role of cDC1s in anti-drug antibodies.

ABSTRACT: Conventional type 1 dendritic cells (cDC1s) are superior in antigen cross-presentation and priming CD8⁺ T cell anti-tumor immunity and thus, are a target of high interest for cancer immunotherapy. Type I interferon (IFN) is a potent inducer of antigen cross-presentation, but, unfortunately, shows only modest results in the clinic given the short half-life and high toxicity of current type I IFN therapies, which limit IFN exposure in the tumor. CD8⁺ T cell immunity is dependent on IFN signaling in cDC1s and preclinical studies suggest targeting IFN directly to cDC1s may be sufficient to drive anti-tumor immunity. Here, we engineered an anti-XCR1 antibody (Ab) and IFN mutein (IFN^mut) fusion protein (XCR1Ab-IFN^mut) to determine whether systemic deli

SUBMITTER: Noe P 

PROVIDER: S-EPMC10628189 | biostudies-literature | 2023

REPOSITORIES: biostudies-literature