NK cell-based immunotherapy proves an attractive adjuvant therapy for leukemia and other malignancies – either stand-alone or in combination with antibodies and tumor-sensitizing drugs. In allogeneic stem cell transplantation, NK cells have shown to mediate graft-versus-leukemia immunity towards recipient tumor cells without attacking normal tissues, leading to graft-versus-host disease.
Numerous studies have demonstrated the ability of NK cells to kill human tumor cell lines ex vivo as well as freshly isolated human tumor cells. Insights into NK cell function in cancer eradication originate from allogeneic transplantation settings. Ruggeri and colleagues demonstrated that NK cell alloreactivity can control relapse of AML without causing graft-versus-host disease (GVHD) in the setting of HLA-mismatched haploidentical allogeneic SCT, which was associated with improved survival. In addition, the NK cell alloreactivity in allogeneic SCT was associated with reduced rates of GVHD. Reduced priming of alloreactive donor T cells as a consequence of NK cell killing of recipient antigen-presenting cells has been postulated as explanation for this observation (ref.). In addition, NK cells were found to exert strong alloimmune responses in immunodeficient mice engrafted with primary human AML (ref.). These results clearly illustrate the anti-tumor potential of alloreactive NK cells in the absence of GVHD. Based on these encouraging results, adoptive transfer of allogeneic NK cells represents a promising approach to induce anti-tumor immunity in AML and other malignancies (ref.).