Research

One of the areas of my research is focused on elucidating the molecular and cellular mechanisms underlying natural and therapeutically induced immune responses to developing and established cancers. Cytotoxic cells (ex: CD8+ T cells and Natural Killer cells) recognize and kill infected and abnormal cells. We are investigating how this process can be inhibited or activated. With this knowledge, we aim to develop and design a new aid for current immunotherapies.

For more than 20 years, my laboratory has been interested in identifying tumor-specific peptides presented by the human leukocyte antigen (HLA) for use as potential targets for immunotherapy. As part of this focus, my laboratory developed methods to discover antibodies that recognize specific peptide/HLA complexes that we named T-cell receptor mimicking (TCRm) antibodies. These molecules share T-cell receptors’ binding selectivity traits while retaining antibodies’ positive attributes. TCRms are highly valued as research tools, and my group has used them extensively to study antigen presentation in tumor cells.

My laboratory has also actively researched and developed other immunotherapeutic agents, including soluble T-cell receptors, multifunctional/multispecific protein-based molecules, and CAR-T cells for targeting HLA loaded with cancer-specific peptides.

These led to our most recent project, the discovery of a TCRm, EXX-1, to Qa-1b/Qdm peptide complex, the NKG2A/CD94 inhibitory receptor ligand. The NKG2A/Qa-1b (HLA-E ortholog) axis is a recently discovered immune checkpoint that suppresses the cytolytic function of NK cells and CD8+ T-cells in the tumor microenvironment. We have shown that EXX-1 is specific for the Qa-1b/Qdm peptide complex and enhances the anti-tumor response against syngeneic tumors in mice