Enhancing BCMA CAR t-cell efficacy through glutamine transporter ASCT2 overexpression
A novel approach to improve BCMA CAR T-cell therapy by engineering cells to overexpress the glutamine transporter ASCT2, enhancing their metabolic fitness and antitumor efficacy in glutamine-deprived environments common in multiple myeloma and other cancers.
Overview
This innovative approach focuses on enhancing the efficacy of BCMA CAR T-cell therapies by reprogramming glutamine metabolism. By engineering CAR T-cells to overexpress the glutamine transporter ASCT2, these cells are better equipped to survive and function in glutamine-deprived tumor microenvironments. This method not only enhances the T-cells' antitumor activity but also improves their persistence in vivo, making it a promising strategy for treating multiple myeloma and potentially other glutamine-dependent cancers.
Technical specifications
Key features:
- Engineering of BCMA CAR T-cells to overexpress the glutamine transporter ASCT2.
- Improved metabolic fitness through enhanced oxygen consumption rate and glycolytic function.
- Increased antitumor activity and persistence in vivo, leading to prolonged survival in mouse models.
- Evaluation in pre-clinical models using murine and human CAR T-cells produced via advanced genetic techniques such as retroviral and Sleeping Beauty transposition.
- Future studies will focus on assessing the lytic capacity, specificity, toxicity, and biodistribution of these engineered T-cells, alongside their impact on the tumor microenvironment.
Technology readiness level
Currently at Technology Readiness Level 5, this solution has been validated in relevant preclinical models. Ongoing studies aim to complete in vitro and in vivo preclinical validations, setting the stage for potential clinical trials.
About University of Navarra
The University of Navarra is a comprehensive private research university based in Pamplona with campuses in San Sebastián and Madrid, pairing academic breadth with strong industry orientation. An integrated university hospital and co-located translational facilities enable rapid clinical validation and access to diverse patient cohorts. The engineering campus in San Sebastián collaborates with an affiliated applied research center and regional manufacturers, offering shared labs, prototyping, and industry placements. Research is backed by competitive European and Spanish funding, including programs from the European Commission and national agencies, plus regional partnerships. A dedicated technology transfer office manages IP, licensing, corporate-sponsored research, and spinout support.
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