Natural killer cells in patients with hematologic malignancies, solid tumors and in recipients of hematopoietic stem cell transplantation

Natural killer cells represent the first line of defense against infections and tumors and can be derived from various sources including: bone marrow, peripheral blood, specific types of human stem cells, and certain cell lines. The functions of natural killer cells are influenced by: several cytokines, activating and inhibitory receptors, as well as other immune cells such as dendritic cells and mesenchymal stem cells. Natural killer cells are attractive candidates for adoptive cellular therapy in patients with hematologic malignancies and solid tumors in addition to recipients of various forms of hematopoietic stem cell transplantation as they enhance antitumor effects without causing graft versus host disease. Several clinical trials have shown safety and efficacy of natural killer cell products obtained from autologous as well as allogeneic sources and used in conjunction with cytotoxic chemotherapy, monoclonal antibodies and novel agents. The following review, which includes extensive literature review on several aspects of natural killer cells, will give particular attention to: the rising role of natural killer cell therapies in patients with malignant hematological disorders, solid tumors and in recipients of stem cell therapies; preparation and manufacture of natural killer cell products; challenges facing the utilization of this form of cellular therapy including evolution of resistance; and maneuvers that can be employed to enhance the efficacy of natural killer cell therapies as well as suggested solutions to resolve the remaining challenges