Docket #: S22-010
Supplementation with inosine improves CAR-T cell metabolism and anti-tumor effects
Researchers at Stanford have developed a method of culture media supplementation with inosine during the chimeric antigen receptor (CAR)-T cell manufacturing process which can alter and enhance CAR-T cell metabolism and anti-tumor functions. Poor efficacy and persistence have hindered the success of CAR-T cell immunotherapy in many patients and tumor types. To address these challenges, this method adds inosine to culture media, resulting in changes in CAR-T cell phenotype and metabolic features. Supplemented CAR-T cells were shown to use inosine as a carbon source, relieving tumor-imposed metabolic restrictions on T cells and leading to increased anti-tumor potency in vitro. The supplemented CAR-T cells can further improve the efficacy of immune checkpoint blockade and adoptive T cell therapies in vivo, prolonging survival in mouse models of solid tumors unable to metabolize inosine. This method can be used during CAR-T cell manufacturing or in further immunotherapy research and development efforts to improve CAR-T cell function.
Stage of Development:
Prototype
Applications
- This method can be used by stakeholders with an interest in improving CAR-T cell efficacy:
- Academic researchers
- Biotech companies
- Pharmaceutical companies
- Cell manufacturing centers
Advantages
- Easy method implementation
- Improved anti-tumor potency of CAR-T cells
- Improved persistence of CAR-T cells in vivo
- Improved efficacy of immune checkpoint blockade and adoptive T cell therapies
Publications
- Dorota D. Klysz, Steven A. Feldman, Crystal L. Mackall, et al.. "Inosine Induces Stemness Features in CAR T cells and Enhances Potency." bioRxiv 2023.04.21.537859.
Related Links
Patents
- Published Application: WO2024010955
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