Mechanisms involved in IL-15 superagonist enhancement of anti-PD-L1 therapy.

ABSTRACT:

Background

Immunotherapy targeting PD-1/PD-L1 fails to induce clinical responses in most patients with solid cancers. N-803, formerly ALT-803, is an IL-15 superagonist mutant and dimeric IL-15RαSushi-Fc fusion protein complex that enhances CD8⁺ T and NK cell expansion and function and exhibits anti-tumor efficacy in preclinical models. Previous in vitro studies have shown that IL-15 increases PD-L1 expression, a negative regulator of CD8⁺ T and NK cell function. Most reported preclinical studies administered N-803 intraperitoneally not subcutaneously, the current clinical route of administration. N-803 is now being evaluated clinically in combination with PD-1/PD-L1 inhibitors. However, the mechanism of action has not been fully elucidated. Here, we examined t

SUBMITTER: Knudson KM 

PROVIDER: S-EPMC6429734 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature