web analytics

Dietary Supplement To Enhance Anti-Tumor Immunity

Interests: Immunooncology
Published:
Lead Inventor: Jing Chen
Print or Save to PDF

SUMMARY

A method to utilize trans-vaccenic acid to enhance CD8+ T cell-mediated anti-tumor immunity through an innovated mechanism promoting T cell activation, infiltration, and survival while reducing exhaustion markers

The Unmet Need: Effective immune modulation in the face of multifaceted resistance mechanisms

  • The field of immunotherapy has rapidly evolved as a promising approach to cancer treatment, harnessing the body’s immune system to target and eliminate malignant cells. However, challenges remain in effectively activating the full spectrum of immune responses, particularly in mobilizing cytotoxic T cells to overcome the immunosuppressive tumor microenvironment. The increasing incidence of resistant or refractory tumors highlights the need for innovative strategies that can support robust T cell-mediated immunity and improve overall treatment outcomes.

  • Current therapeutic approaches have notable limitations that hinder long-term efficacy. Many existing treatments rely heavily on pathways that are susceptible to regulatory checkpoints which can dampen T cell activation and promote exhaustion. Additionally, the complex network of inhibitory signals within tumors often prevents adequate infiltration of immune cells, limiting their potential to sustain anti-tumor activity. These issues are compounded by the challenges of overcoming inherent metabolic constraints and the elusive nature of effective immune modulation in the face of multifaceted resistance mechanisms.

The proposed solution: Strategy to use trans-vaccenic acid to activate T cells and reverse tumor cell-dependent inhibition of T cells

  • The faculty inventor leveraged trans-vaccenic acid (TVA), a naturally occurring trans fatty acid found in dairy and human milk, to enhance CD8⁺ T cell anti-tumor responses. TVA binds to a G protein-coupled receptor, rapidly increasing cAMP levels to activate protein kinase A and CREB signaling within hours, followed by later activation of the JAK-STAT1 pathway that boosts interferon-γ expression. This cascade promotes T cell activation, tumor infiltration, and survival while reducing exhaustion marker expression. Additionally, TVA counteracts the immunosuppressive influence of short-chain fatty acids by antagonizing receptors such as GPR43, thereby potentiating the efficacy of T cell-based therapies.

  • The approach is differentiated by its reliance on external signaling, bypassing conventional mechanisms like the PD-L1–PD-1 axis. Its unique dual-phase cascade—delivering immediate and sustained T cell stimulation—leads to enhanced immune responses across diverse cancer models. By reversing T cell exhaustion and supporting prolonged activation without dependence on cellular uptake pathways, the strategy offers a synergistic means to improve the performance of checkpoint inhibitors, CAR-T therapies, and other immunotherapies, representing a significant advancement in cancer treatment.

ADVANTAGES

ADVANTAGES

  • Enhances CD8⁺ T cell activation, infiltration, and survival against tumors

  • Triggers a rapid GPCR-mediated signaling cascade, boosting cAMP, PKA, and CREB activity followed by JAK-STAT1 activation to increase IFN-γ expression

  • Reduces T cell exhaustion by lowering markers like PD-1 and LAG-3, thereby improving immune response longevity

  • Antagonizes immunosuppressive effects of short-chain fatty acids via GPR43, enhancing the efficacy of other T cell-based therapies

  • Operates independently of the PD-L1–PD-1 axis, allowing synergistic effects with checkpoint inhibitors and various immunotherapeutic approaches

APPLICATIONS

  • Immune checkpoint blockade therapy

  • CAR-T therapy adjuvant

  • BiTEs treatment enhancer

  • T cell activation booster

PUBLICATIONS