The Technology
Cancer immunotherapy shows poor clinical results in many cancer types, due to deprivation of required metabolic nutrients from T cells – tumors compete with T cells for the same essential nutrients including glucose and amino acids. Once T cells arrive from the blood stream at the tumor site they become exposed to starvation conditions under which they need to undergo activation. T cell starvation at the tumor microenvironment was shown to hamper T cell activation, differentiation and killing abilities. This results in T cell suppression and anergy, leading to tumor escape. Currently there is no known proposed solution to overcome metabolic suppression of T cells. Attempts have been made to prevent the degradation of a single T cell essential metabolite at the tumor microenvironment – the amino acid L-arginine. However, the newly developed arginase inhibitor (INCB001158, Calithera Biosciences) increases arginine levels for both tumor and T cells. As many tumors depend on external arginine supply with the loss of the ASS1 gene required for arginine synthesis, other companies have taken the opposite approach to decrease arginine blood levels to starve tumors from arginine (Pegargiminase, Polaris Pharma). This illustrates the problem that metabolites should be specifically delivered to T cells and not the tumor. Another limitation is that metabolic T cell suppression encompasses several metabolites and not just arginine. The innovative nanotechnology-based approach to overcome metabolic T cell suppression in cancer immunotherapy: delivering essential metabolic nutrients to T cells via nanoparticle encapsulation. The nanoparticles are specifically fed to T cells thus ensuring specific delivery of essential metabolites to T cells and not tumor cells. The metabolites gradually release from the nanoparticles in a controlled release fashion, ensuring essential nutrient supply when the T cells enter the starvation conditions present at the tumor microenvironment. This food reservoir installed inside the T cells enables them to undergo activation when they meet their tumor target and unleashes them from the metabolic suppression imposed by the tumor.
Advantages
- Supply T cells any metabolite that is needed, including combinations of metabolites
- metabolites are supplied only to the T cells and not the tumor
- a potential drug against all cancer types
- synergizes with all existing immunotherapy drugs, particularly immune checkpoint inhibitors, CAR T therapy and TIL therapy
Applications and Opportunities
- Cancer immunotherapy
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