Myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML) are debilitating blood (hematologic) cancers characterized by the accumulation of somatic mutations in clonally expanded hematopoietic stem and progenitor cells (cells that can differentiate into other types of mature blood cells). To date, the only potentially curative treatment for patients with MDS and most forms of AML is allogenic hematopoietic stem cell transplant, which is effective in only up to 50 percent of cases and is associated with substantial morbidity and mortality. Thus, novel therapies with curative potential are urgently needed.

The adoptive transfer of naturally occurring T cells directed against cancer neoantigens — proteins that are predominantly encoded by genes harboring cancer-specific point mutations — can mediate complete regression of metastatic melanoma and select cases of metastatic epithelial cancer. However, this therapy has not yet been successfully used in patients suffering from MDS, AML, and other hematological malignancies.

The main objectives of Dr. Leko’s research are (1) to establish the prevalence and characteristics of T cell responses against potential tumor neoantigens in patients with hematological cancers, and (2) to develop clinical protocols involving the adoptive transfer of neoantigen-reactive T cells for patient treatment.