Natural Killer cell therapy against AML

Dolstra, Harry 2016.jpg

Harry Dolstra (photo up), Mieke Roeven and Michel Schaap, themes Cancer development and immune defense and Rare cancers published in Clinical Cancer Research their first-in-human clinical trial results with Natural Killer cell infusion in older Acute myeloid leukemia patients.

Acute myeloid leukemia (AML) is prevalent in older adults with a mean age of 69 years. Current treatment consists of intensive chemotherapy, hypomethylating agents, low-dose cytarabine or supportive care. Although morphologic complete remission can be achieved in 40-60% of older patients, most patients relapse resulting in a 5-year overall survival of about 10-20%. Therefore, development of novel and tolerable adjuvant therapies are needed. Allogeneic natural killer (NK) cells have been adoptively transferred with promising clinical results. In this Clinical Cancer Research paper, we report the first-in-human study exploiting an unique scalable NK cell product generated ex vivo from CD34+ hematopoietic stem and progenitor cells (HSPCs) from partially HLA-matched umbilical cord blood units.We demonstrate that HSPC-NK cell products containing up to 30x106 NK cells/kg can be safely infused after lymphodepleting chemotherapy. HSPC-NK cells were well tolerated and no graft-versus-host disease nor toxicity was observed. Importantly, we demonstrate that infused HSPC-NK cells engraft, home to the bone marrow and undergo in vivo maturation. Additionally, we observed a temporary decrease in minimal residual disease (MRD) in the bone marrow in some patients. This HSPC-NK cell-based immunotherapy should be further explored in combination with cytokines to boost in vivo NK cell expansion or tumor targeting strategies to maximize clinical efficacy. Thereby, it could be an adjuvant therapy to eradicate MRD in AML patients following chemotherapy or treatment with hypomethylating agents, and serve as consolidating therapy or even as bridge towards non-myeloablative allogeneic stem cell transplantation. Our findings therefore pave the way towards personalized HSPC-NK cell immunotherapy against AML as well as other cancer types.

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Mieke Roeven                                            Michel Schaap

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