Allogeneic hematopoietic stem cell transplantation (alloSCT) is a curative treatment for high-risk leukemia. The donor's immune cells, which are transferred to the recipients, can eradicate leukemia. This so-called graft-versus leukemia effect (GVL) has been the subject of intense study in my laboratory and elsewhere. My research aims to find ways to harness this GVL to cure leukemia through three approaches.

 

The first is to improve the results of transplants for people with leukemia through low-dose cytokine therapy. I am conducting a clinical study to evaluate interferon-gamma (IFN-γ) to treat post-transplant relapse (NCT04628338), collaborating with Dr. Warren Shlomchik, based on his pre-clinical data supporting IFN-γ sensitizes leukemic cells to T-cell killing.

 

The second is to identify the mechanisms of how the leukemic cells escape from immune attacks. I have been investigating cellular and humoral biomarkers associated with post-transplant relapse and GVL. We aim to find clinically-applicable assays to monitor the post-transplant immune microenvironment favorable to GVL.

 

The third approach is to develop donor-derived adoptive T cell therapy, which directly boosts the GVL. Donor-derived T cells may recognize various antigens, including human leukocyte antigens (HLAs), minor histocompatibility antigens (miHAs), overexpressed leukemia-associated antigens, or neoantigens. Our laboratory aims to establish new T cell therapies targeting these antigens in alloSCT. We have been currently engaged in developing the miHA-specific T cell therapy in alloSCT.

 

My ultimate goal is to find ways to create an anti-leukemia immunotherapy utilizing the patient's own immune system and thus avoid the complication of alloSCT altogether.