Abstract
Natural killer (NK) cells are a population of cytotoxic innate lymphocytes that evolved prior to their adaptive counterparts and constitute one of the first lines of defense against infected/mutated cells. Several studies have shown that in patients with acute leukemia given haploidentical hematopoietic stem cell transplantation, donor-derived NK cells play a key role in the eradication of cancer cells. The antileukemic effect is mostly related to the presence of “alloreactive” NK cells, that is, mature KIR+ NK cells that express inhibitory KIR mismatched with HLA class I (KIR-L) of the patient. A genotypic analysis detecting KIR B haplotype and the relative B content is an additional donor selection criterion. These data provided the rationale for implementing phase I/II clinical trials of adoptive infusion of either selected or ex vivo-activated NK cells, often from an HLA-mismatched donor. In this review, we provide a historical perspective on the role played by NK cells in patients with acute leukemia, focusing also on the various approaches to adoptive NK cell therapy and the unresolved issues therein. In addition, we outline new methods to enhance NK activity, including anti-KIR monoclonal antibody, bi-/trispecific antibodies linking NK cells to cytokines and/or target antigens, and CAR-engineered NK cells.
Highlights
A substantial body of evidence has emerged delineating the role of natural killer (NK) cells in the immunosurveillance of/immune response to leukemia as well as its therapeutic treatment
NK cells play a key role in the immune response against cancer and are important in haplo hematopoietic stem cell transplantation (HSCT) as a treatment of high-risk leukemia in both adult and pediatric patients
Their antileukemic effect is mostly related to the presence of “alloreactive” NK cells, though an important role is played by certain activating killer cell immunoglobulin-like receptors (KIR) upon interaction with their HLA class I ligand (C2 alleles)
Summary
A substantial body of evidence has emerged delineating the role of natural killer (NK) cells in the immunosurveillance of/immune response to leukemia as well as its therapeutic treatment. Inhibitory receptors which recognize HLA class I molecules play an important role in their function These inhibitory killer cell immunoglobulin-like receptors (KIR) permit NK cells to recognize “self” and provide inhibitory signals to preclude killing of the target cell [2]. In a hematopoietic stem cell transplantation (HSCT) setting, donor NK cell inhibitory receptors mismatched for cognate HLA class I ligand play an important role in the graft-versus-leukemia (GvL) effect [5]. These cells may be uniquely poised to enhance GvL without eliciting graft-versus-host disease (GvHD) because healthy nonhematopoietic tissues lack activating receptor ligands present on tumor cells [6]. We describe the key role played by NK cells in the setting of haploidentical (haplo) HSCT as protection against leukemia recurrence, review the adoptive transfer of NK cells for leukemia immunotherapy with or without HSCT, and enumerate the novel approaches being investigated to enhance NK activity
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
