Natural Killer Cell-Mediated Cellular Therapy of Hematological Malignancies

Our understanding on the mechanisms of graft versus tumor/leukemia (GvT/GvL) and graft versus host (GvH) effects has tremendously evolved within the past decades. During the search for a mechanism that augments GvT/GvL without increasing GvH effects, natural killer (NK) cells have clearly attracted attention. Current approaches of NK cell immunotherapy for hematological malignancies involve using methods for in vivo potentiation of NK cell proliferation and activity; adoptive transfer of NK cells from autologous and allogeneic sources [cord blood mononuclear cells, peripheral blood mononuclear cells, CD34⁺ stem cells] and NK cell lines; and genetic modification of NK cells. Several cytokines, including interleukin-2 and interleukin-15 take part in the development of NK cells and have been shown to boost NK cell effects both in vivo and ex vivo. Monoclonal antibodies directed towards certain targets, including stimulating CD16, blockade of NK cell receptors, and redirection of cytotoxicity to tumor cells via bi- or tri-specific engagers may promote NK cell function. Despite the relative disappointment with autologous NK cell infusions, the future holds promise in adoptive transfer of allogeneic NK cells and the development of novel cellular therapeutic strategies, such as chimeric antigen receptor-modified NK cell immunotherapy. In this review, we summarize the current status of NK cell-related mechanisms in the therapy of hematologic malignancies, and discuss the future perspectives on adoptive NK cell transfer and other novel cellular immunotherapeutic strategies.