Persistent Memory T-Cell Responses to Cancer and Infectious-disease Antigens by Manipulation of Amino Acid-catabolism Pathways

Abstract

Researchers at the University of California, Davis, have created a technology that uses engineered polynucleotides to deliver both an antigen and an enzyme that breaks down amino acids. This approach is designed to boost long-lasting memory T-cell responses, providing stronger protection against infectious diseases and cancer.

Full Description

The invention provides compositions and methods leveraging co-expression of infectious disease or tumor-associated antigens alongside enzymes involved in amino acid catabolism pathways—such as indoleamine 2,3-dioxygenase 1 (IDO1) or arginase 1—to rebalance immune responses. This approach enhances long-lived memory CD4+ T-cell responses while modulating effector T-cell activity, leading to improved vaccine efficacy and immunotherapy outcomes against diseases including viral infections (e.g., SARS-CoV-2, HIV) and cancers.

Applications

• Advanced vaccines for viral infectious diseases, including SARS-CoV-2, HIV, influenza, and hepatitis C. 
• Immunotherapies targeting cancers via tumor-associated antigens and neoantigens. 
• Combination vaccine platforms incorporating immunoregulatory enzymes for improved efficacy. 
• Therapeutic interventions for bacterial, fungal, protozoan, and helminthic infections. 
• Development of diagnostic biomarker profiles and monitoring tools to accurately track vaccination or treatment success.

Features/Benefits

• Induces robust and durable memory CD4+ T cell responses, shifting the immune profile toward lasting protection rather than transient effector function.
• Rebalances immune responses by enhancing amino acid catabolism, promoting protective memory T cells over short-lived effector T cells. 
• Reduces production of detrimental inflammatory cytokines such as IFN-γ, potentially minimizing immunopathology and systemic adverse effects. 
• Encodes multiple antigens and catabolic enzymes, expanding versatility for targeting various infectious diseases and cancers. 
• Addresses short-lived and suboptimal immune memory generated by conventional vaccines.

Patent Status