Evaluation of Combination Strategies for the A_2AR Inhibitor AZD4635 Across Tumor Microenvironment Conditions via a Systems Pharmacology Model.

ABSTRACT:

Background

Adenosine receptor type 2 (A_2AR) inhibitor, AZD4635, has been shown to reduce immunosuppressive adenosine effects within the tumor microenvironment (TME) and to enhance the efficacy of checkpoint inhibitors across various syngeneic models. This study aims at investigating anti-tumor activity of AZD4635 alone and in combination with an anti-PD-L1-specific antibody (anti-PD-L1 mAb) across various TME conditions and at identifying, via mathematical quantitative modeling, a therapeutic combination strategy to further improve treatment efficacy.

Methods

The model is represented by a set of ordinary differential equations capturing: 1) antigen-dependent T cell migration into the tumor, with subsequent proliferation and differentiation into effector T c

SUBMITTER: Voronova V 

PROVIDER: S-EPMC7962275 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature