Alum-anchored intratumoral retention improves the tolerability and antitumor efficacy of type I interferon therapies

Significance Type I IFNs hold considerable promise for the treatment of cancer, but it is unclear how best to activate this pathway pharmacologically. We compared the intratumoral administration of two type I IFN subtypes and three design strategies (IFN, extended half-life IFN, and intratumorally retained IFN) in several immunocompetent mouse tumor models. Intratumoral retention of type I IFNs greatly improved treatment efficacy and decreased toxicity. Intratumorally retained type I IFNs were also effective in combination immunotherapies. However, combination therapies with excessive cytokine signaling harmed adaptive memory formation. Intratumoral retention is a promising strategy for type I IFNs, but warrants careful consideration of IFN subtype, tumor phenotype, and agents for combination therapy.

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