Anchoring of intratumorally administered cytokines to collagen safely potentiates systemic cancer immunotherapy.

ABSTRACT: The clinical application of cytokine therapies for cancer treatment remains limited due to severe adverse reactions and insufficient therapeutic effects. Although cytokine localization by intratumoral administration could address both issues, the rapid escape of soluble cytokines from the tumor invariably subverts this effort. We find that intratumoral administration of a cytokine fused to the collagen-binding protein lumican prolongs local retention and markedly reduces systemic exposure. Combining local administration of lumican-cytokine fusions with systemic immunotherapies (tumor-targeting antibody, checkpoint blockade, cancer vaccine, or T cell therapy) improves efficacy without exacerbating toxicity in syngeneic tumor models and the Braf^V600E /Pten^fl/fl

SUBMITTER: Momin N 

PROVIDER: S-EPMC7811803 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature