Development of a drug delivery system for efficient sting agonist and anti-ox40 combination therapy

Abstract

Combination therapy with immunologic adjuvants presents a promising method to improve the efficacy of anti-OX40 cancer immunotherapy. Previous studies have shown that adjuvant-induced inflammatory signals and T cell OX40 expression can enhance OX40 stimulation by anti-OX40 mAb. However, these studies have not taken into consideration the timecourse of OX40 and expression and activity, which is a critical factor in the strength of OX40 signaling. As T cells upregulate OX40 on their surface with delayed kinetics upon activation, a delay should exist between the delivery of the activating adjuvant and anti-OX40 mAb as well. This study proposes a hydrogel-based release system for the co-delivery of STING agonists and anti-OX40 mAb. The pore size of the hydrogel system is optimized to take advantage of the size difference of the two payloads, producing a burst release of STING agonists and a delayed slow release of mAb. Local injection of this system at the tumor site will allow for anti-OX40 delivery when intratumoral OX40 expression is at its peak, maximizing therapeutic efficiency of combination therapy.