T Cell Receptors Interactions with HLA



Jack Bui, MD, PhD
Director, Stem Cell Processing Laboratory
Associate Professor, UC San Diego School of Medicine

Gerald P. Morris, MD, PhD
Associate Professor of Pathology
Director, Immunogenetics and Transplantation Laboratory
University of California, San Diego

Drs. Bui and Morris have worked together to develop novel approaches for cancer immunotherapies that take advantage of their expertise in T cell receptors (TCRs) and their interactions with human leukocyte antigen (HLA) complexes on the surface of tumor cells. The HLA complexes on tumor cells may display unique neoantigens or immunogenic peptides that can be recognized by the body's own T cells. This project will identify viral peptides that can be displayed by tumor cells so that the body's own virus-fighting T cells can kill tumor cells.

The Need

In cancer patients, immune therapy cannot proceed optimally unless a population of T cells can be found that can be induced to recognize and eliminate the cancer. Many T cells in cancer patients are either incapable of recognizing tumor antigens or exhausted and incapable of mounting an effective response. This project examines virus-specific T cells as a reservoir for tumor killing.

The Opportunity

The unique idea for this project involves re-purposing virus-specific T cells for tumor therapy. All patients have T cells specific for common viruses that inhabit the blood and also can patrol tumor tissue. Drs. Bui and Morris will identify viral peptides that can be used to coat tumor cell surfaces to make the tumor cell resemble an infected cell. As such, the body's own virus-specific T cells will recognize and kill the tumor cells. Massive killing of the tumor cells by these T cells will serve as a vaccine to activate new, non-exhausted tumor-specific T cells that sustain the immune response.

The Impact
This work can result in a novel treatment of cancer patients using viral peptides. The specific peptides identified in the research can be packaged into a peptide vaccine that can be delivered directly into the tumor. This could have efficacy in all types of cancer that can be accessed for intratumoral delivery of the vaccine, including head and neck, breast, prostate, melanoma, pancreatic, and lung cancer. The peptides can also be used to develop a blood test that can identify patients who have the highest levels of virus-specific T cells, thereby providing a biomarker for inclusion into a clinical trial.