Durable antitumor response via an oncolytic virus encoding decoy-resistant IL-18.

ABSTRACT:

Background

Interleukin-18 (IL-18), or interferon (IFN)-γ-inducing factor, potentiates T helper 1 and natural killer cell activation as well as CD8⁺ T-cell proliferation. Recombinant IL-18 has displayed limited clinical efficacy in part due to the expression of the decoy receptor, IL-18 binding protein (IL-18BP). A series of IL-18 variants that are devoid of IL-18BP binding, termed DR18 (decoy-resistant IL-18), was developed via directed evolution. We tested DR18 using oncolytic adenovirus (oAd) as a platform for delivery in syngeneic mouse tumor models.

Methods

oAd harboring wild-type IL-18 or DR18 (oAdDR18) was constructed by inserting IL-18 mutant into modified oAd backbone with Ad5/3 chimeric fiber. The delivery effect and IFN-γ induction were determined by ELI

SUBMITTER: Cheng Y 

PROVIDER: S-EPMC11624705 | biostudies-literature | 2024 Dec

REPOSITORIES: biostudies-literature