Order of administration of combination cytokine therapies can decouple toxicity from efficacy in syngeneic mouse tumor models.

ABSTRACT: In combination cancer immunotherapies, consideration should be given to designing treatment schedules that harmonize with the immune system's natural timing. An efficacious temporally programmed combination therapy of extended half-life interleukin 2 (eIL2), tumor targeting antibody, and interferon (IFN) α was recently reported; however, tumor-ablative efficacy was associated with significant toxicity. In the current work, altering the order and timing of the three agents is shown to decouple toxicity from efficacy. Delaying the administration of eIL2 to be concurrent with or after IFNα eliminates toxicity without affecting efficacy in multiple syngeneic tumor models and mouse strains. The toxicity resulting from eIL2 administration before IFNα is dependent on multiple systemic inflammator

SUBMITTER: Rothschilds A 

PROVIDER: S-EPMC6492973 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature