Composition of NY-ESO-1-Specific T Cell Receptors Restricted on Multiple Major Histocompatibility Complex Molecules

Tech ID: 29913 / UC Case 2019-008-0

Summary

Researchers at the UCLA Department of Microbiology, Immunology, and Molecular Genetics have isolated T cell receptors (TCRs) specific for NY-ESO-1 epitopes presented by four MHC molecules, and developed novel approaches to extend TCR gene therapies targeting NY-ESO-1 using these TCRs.

Background

The αβ T cell receptor (TCR) determines the unique specificity of each nascent T cell. Upon assembly with CD3 signaling proteins on the T cell surface, the TCR surveils peptide ligands presented by major histocompatibility complex (MHC) molecules on the surface of nucleated cells. The specificity of the TCR for a peptide-MHC complex is determined by both the presenting MHC molecule and the presented peptide. Infected and cancerous cells present peptides that are recognized by CD8+ T cells as foreign or aberrant, resulting in T cell-mediated killing. Tumor-specific TCR gene transfer enables specific and potent immune targeting of tumor antigens. Due to the prevalence of the HLA-A2 major MHC, the majority of TCR gene therapy trials targeting public antigens have employed HLA-A2-restricted TCRs, limiting this approach to patients expressing HLA-A2 allele. Therefore, there is a need for broad and safe application of public antigen-targeted TCR gene therapies.

Innovation

The NY-ESO-1 is a tumor-specific, immunogenic public antigen that is expressed across an array of tumor types, but it is susceptible to escape when targeted through a single HLA subtype. To broaden the clinical utility of NY-ESO-1 as a TCR gene therapy target, researchers at UCLA have identified novel TCRs that target NY-ESO-1 epitopes presented by common MHC alleles other than HLA-A2. These researchers propose that targeting multiple NY-ESO-1 epitopes will enable treatment of a larger patient set and may render treatment more robust toward tumor escape.

Applications

Cancer immunotherapy

Advantages

  • Targets NY-ESO-1 in a broader array of HLA haplotypes 
  • Targets multiple epitopes presented by multiple MHC alleles is more desirable for successful immunotherapy
  • Targets multiple epitopes derived from a tumor-specific public antigen may be a promising alternative to targeting neoepitopes in cancers with low mutational burden

Patent Status

Patent Pending

Contact

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Inventors

  • Witte, Owen N.

Other Information

Keywords

Cancer, immunotherapy, therapeutics, T cell, T cell receptor, TCR, NY-ESO-1, major histocompatibility complex, MHC

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