Targeting of pro-immunostimulants to tumor environments
Cancer treatments could be optimized through more effective ways of targeting immunostimulants to tumor environments. Current immunotherapies are limited to direct intra-tumoural infusion, due to severe inflammatory toxicity that results from systemic routes of administration. Directed Enzyme Prodrug Therapy (DEPT) is an approach that couples a drug with a substrate, together the prodrug, where the drug is not active until the substrate has been cleaved off. A DEPT approach for the delivery of an immunostimulant to a cancerous region would prevent problems associated with inflammatory toxicity, providing a localized immune response directed towards the cancerous region.
Researchers at WSU have developed a pro-immunostimulant for cancer therapy that is only released in relevant concentrations in regions where there is cancerous activity. Once released it activates a robust, innate immune response in the region through enzyme directed substrate cleavage and immunostimulant release. A few robustly activated immune cells go on to activate bystander immune cells in the tumor microenvironment, resulting in a localized immune response. This not only allows for directed therapy but also greatly reduces off target cytotoxicity that is common in this class of therapeutics – as activated immune cells can only activate more immune cells, we are not dropping cytotoxic loads that can damage non-cancerous cells. Because this treatment relies on the activation/enhancement of natural mechanisms, it can be used in conjunction with existing chemotherapies.
Applications and Advantages
• Targeted activation of the immune response that prevents problems associated with inflammatory toxicity due to systemic approaches
• Activates robust natural tumor suppression pathways, allowing use in conjunction with existing chemotherapies
• Takes advantage of the bystander effect by activating a few immune cells (in a cancerous environment) which go on to activate other immune cells in that environment