Enhancing CAR-T cell therapy by targeting lactate metabolism in solid tumors
This innovative approach aims to enhance CAR-T cell therapy in solid tumors by reducing lactate levels in the tumor microenvironment through mitochondrial enhancement. The strategy involves genetic and pharmacological methods to improve immune cell function and tumor response.
Overview
The proposed solution addresses the challenge of immunosuppression in the tumor microenvironment (TME) caused by high lactate levels, which inhibit immune cell functions. By targeting lactate metabolism, this research seeks to enhance CAR-T cell therapy in solid tumors. The approach involves restoring mitochondrial metabolism in tumor cells to limit lactate production, thereby reducing immune suppression and enhancing the effector functions of CD8 and CAR-T cells.
Technical specifications
The core of this solution is based on two strategies for enhancing mitochondrial function in tumor cells to reduce lactate production:
- Genetic Enhancement: Utilizing a knock-in of PGC1a, a master regulator of mitochondrial biogenesis, in tumor cells to stimulate mitochondrial metabolism and decrease lactate levels.
- Pharmacological Activation: Employing activators such as TEPP46 and DASA58 to enhance mitochondrial metabolism via activation of PKM2, thereby reducing lactate production in tumor cells.
These approaches are tested in mice models with melanoma cell lines, observing tumor growth, survival, and immune cell activation post CAR-T cell therapy.
Technology readiness level
This research is at Technology Readiness Level 3. Initial testing has been conducted in laboratory settings using animal models. Further validation and development are required to transition this solution towards clinical trials and potential commercialization.
About University of Minnesota
The University of Minnesota is a flagship, comprehensive public research university spanning multiple campuses, with a large research enterprise and clinical integration. Industry engages through co-located labs on the Twin Cities campuses, access to an academic health system for clinical translation, and pilot and field-testing facilities that speed scale-up. A statewide extension network and outreach centers provide real-world sites and data partnerships across Minnesota, while proximity to a dense medtech and Fortune 500 corridor enables frequent collaboration. Research is supported by competitive federal funding, including NIH, NSF, DOE, USDA, and DoD. A dedicated technology transfer office manages IP, licensing, sponsored research agreements, and startup incubation to speed commercialization.
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