Cytokine induced memory-like NK cell immunotherapy to target post transplant relapse
Dana-Farber Cancer Institute
Project Term: July 1, 2021 - June 30, 2026
Acute myeloid leukemia (AML), myelodysplastic syndrome (MDS) and myeloproliferative neoplasms (MPN) are some of the most common blood cancers in adult patient population. Unfortunately despite recent advances less than half of these patients are cured with the current treatment approaches. Hematopoietic stem cell transplant remains a curative option, however a significant number of patients relapse after the transplant and there are currently no effective and safe treatment options available for these patients. In recent years we have witnessed a revolution in developing novel treatments aimed at targeting cancer by immune cells like T cells. More recently, genetically modified T cells called CAR T cells have proven quite effective against various lymphoid cancers. However, CAR T cells have proven significantly less effective in patients with AML/MDS or MPN. Our work helped discover that another type of immune cell, memory-like Natural Killer (NK) cells, have enhanced activity against AML/MDS and MPN tumor cells. Use of memory-like NK cells was safe and associated with very promising results in our small clinical trial in patients with advanced AML. Infusion of these cells was safe and induced complete remission (CR) in more than 50% of the patients. We are now evaluating use of memory-like NK cells in patients with AML/MDS/MPN who have relapsed after stem cell transplantation. Patients who relapse after stem cell transplantation are typically treated with what is called donor lymphocyte infusion (DLI), but the response rates are typically low and often complicated by graft versus host disease (GVHD) causing significant morbidity and mortality. With our current trial using memory-like NK cells in these patients we are expecting to demonstrate superior efficacy without causing GVHD. If successful, this work could lead to the development of a safer and more effective treatment option for these patients who otherwise have extremely limited survival.