Fatty acids In T Cell-Based Cancer Therapies

SUMMARY

Enhanced anti-tumor immunity through immunomodulation is achieved by fatty acids that activate CD8+ T cells, thereby improving cancer immunotherapy efficacy and reducing T-cell exhaustion.

The Unmet Need: Limited effectiveness of current cancer immunotherapies due to T-cell dysfunction and exhaustion

• Current cancer immunotherapies, including immune checkpoint inhibitors and CAR T-cell therapies, are often limited by inadequate T-cell activation and the development of T-cell exhaustion, which diminishes anti-tumor responses and restricts clinical benefit across many patients.
• Advances in immunometabolism and molecular immunology have created opportunities to identify novel bioactive compounds that modulate immune cell functions, offering potential to enhance existing immunotherapies by improving T-cell performance and persistence in the tumor microenvironment.

The Proposed Solution: Use of selected fatty acids to modulate T-cell activity via distinct GPCR-mediated signaling pathways

• The faculty inventor developed a method utilizing trans-vaccenic acid (TVA), nervonic acid (NVA), and cis-11,14-eicosadienoic acid (EDA) as immunomodulatory agents identified from a screen of 62 fatty acids targeting CD8+ T cells. These fatty acids enhance T-cell function, increase tumor infiltration, and mitigate exhaustion through complementary G protein-coupled receptor pathways. Unlike prior approaches, this strategy leverages multiple distinct molecular mechanisms for synergistic enhancement of anti-tumor immunity. Initial validation in mouse models demonstrates improved immunotherapy outcomes. Further development includes derivative compounds with improved potency and exploration of dietary supplement formulations for translational application.

ADVANTAGES

• Enhanced CD8+ T-cell activation and function
• Reduced T-cell exhaustion in tumor microenvironment
• Complementary mechanisms via distinct GPCR pathways
• Potential biomarkers for therapy response prediction
• Versatile formulation options including dietary supplements

APPLICATIONS

• Adjunct therapy with immune checkpoint inhibitors
• Enhancement of CAR T-cell cancer treatments
• Immunometabolic support through dietary supplementation