Abstract
Natural killer (NK) lymphocytes are an integral component of the innate immune system and represent important effector cells in cancer immunotherapy, particularly in the control of hematological malignancies. Refined knowledge of NK cellular and molecular biology has fueled the interest in NK cell-based antitumor therapies, and recent efforts have been made to exploit the high potential of these cells in clinical practice. Infusion of high numbers of mature NK cells through the novel graft manipulation based on the selective depletion of T cells and CD19+ B cells has resulted into an improved outcome in children with acute leukemia given human leucocyte antigen (HLA)-haploidentical hematopoietic transplantation. Likewise, adoptive transfer of purified third-party NK cells showed promising results in patients with myeloid malignancies. Strategies based on the use of cytokines or monoclonal antibodies able to induce and optimize NK cell activation, persistence, and expansion also represent a novel field of investigation with remarkable perspectives of favorably impacting on outcome of patients with hematological neoplasia. In addition, preliminary results suggest that engineering of mature NK cells through chimeric antigen receptor (CAR) constructs deserve further investigation, with the goal of obtaining an “off-the-shelf” NK cell bank that may serve many different recipients for granting an efficient antileukemia activity.
Highlights
Natural killer (NK) cells are cytotoxic and cytokine-producing components of innate lymphoid cells (ILCs), playing important roles in antiviral and antitumor defense [1,2]
CD94:natural killer group 2A (NKG2A) is considered a sensor of the overall amount of human leucocyte antigen (HLA) class I expressed on the cell surface
In high-risk elderly patients with acute myeloid leukemia (AML) infused with highly purified alloreactive NK cells from haploidentical donors after Cy/Flu immunosuppressive chemotherapy followed by in-vivo IL-2 administration, no NK cell-related toxicity, including graft-vs-host disease (GvHD), was observed [135]
Summary
Natural killer (NK) cells are cytotoxic and cytokine-producing components of innate lymphoid cells (ILCs), playing important roles in antiviral and antitumor defense [1,2]. ILCs represent a heterogeneous group of immune cells that are mainly localized at epithelial surfaces, where they maintain tissue homeostasis and quickly respond to pathogen invasion by mediating appropriate immune responses They develop from a common lymphoid progenitor but, differently from T and B lymphocytes, lack the expression of antigen receptors encoded by rearranged genes. NK cells preserve tolerance towards surrounding healthy cells, mainly through inhibitory receptors recognizing self-major histocompatibility complex (MHC) class I molecules In humans, they are represented by killer immunoglobulin-like receptors (KIRs) and CD94:natural killer group 2A (NKG2A), specific for classical and nonclassical HLA class I molecules, respectively. We first describe the NK cell biology with the various receptor/ligand interactions governing their capability to attack malignant cells, of hematological origin, and the different immunotherapeutic approaches employing autologous or allogeneic NK cells, in transplantation and non-transplantation setting, either un-activated or potentiated by different systems including cell engineering
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