Central Carbon Metabolite Based Polymers for Immunotherapy

Inhibition of glycolysis or glutaminase pathway is an effective strategy to prevent cancer cell growth in vitro and in vivo. However, these pathways are also utilized by immune cells to mount responses against cancer cells, and therefore, utilizing, immunotherapies in the presence of such inhibitors is challenging. Thus, there is a need for technologies that can restart metabolic pathways of immune cells in the presence of metabolic inhibitors and improve methods of treating a disease or disorder by combining immunotherapy with metabolic inhibition.

 

Researchers at Arizona State University introduced an innovative approach to cancer immunotherapy by enhancing the function of dendritic cells (DCs) and T cells. It focuses on overcoming metabolic exhaustion through the delivery of critical metabolites using microparticles formed from compounds like fructose 1,6-bisphosphate (F16BP) and polyethylene glycol-succinate (PEGS). These microparticles are designed to bypass metabolic inhibitors and sustain immune cell activation and function. Through in vitro and in vivo experiments, inventors have shown that F16BP particles can rescue activation and glycolysis of DCs in the presence of PFK15, a glycolysis pathway inhibitor. Similarly, PEGS particles can rescue activation, mitochondrial respiration and glycolytic capacity of DCs from the effect of CB-839, a glutaminase1-mitochondrial respiration inhibitor. Administering the particles in a mouse model of melanoma in conjunction with metabolic inhibitors leads to increase in proinflammatory immune response, decrease in anti-inflammatory immune response, and reduced tumor size.

 

Potential Applications

Benefits and Advantages

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