Revving up Natural Killer Cells and Cytokine-Induced Killer Cells Against Hematological Malignancies

Abstract

Natural killer (NK) cells belong to innate immunity and exhibit cytolytic activity against infectious pathogens and tumor cells. NK-cell function is finely tuned by receptors that transduce inhibitory or activating signals, such as killer immunoglobulin-like receptors, NK Group 2 member D (NKG2D), NKG2A/CD94, NKp46, and others, and recognize both foreign and self-antigens expressed by NK-susceptible targets. Recent insights into NK-cell developmental intermediates have translated into a more accurate definition of culture conditions for the in vitro generation and propagation of human NK cells. In this respect, interleukin (IL)-15 and IL-21 are instrumental in driving NK-cell differentiation and maturation, and hold great promise for the design of optimal NK-cell culture protocols. Cytokine-induced killer (CIK) cells possess phenotypic and functional hallmarks of both T cells and NK cells. Similar to T cells, they express CD3 and are expandable in culture, while not requiring functional priming for in vivo activity, like NK cells. CIK cells may offer some advantages over other cell therapy products, including ease of in vitro propagation and no need for exogenous administration of IL-2 for in vivo priming. NK cells and CIK cells can be expanded using a variety of clinical-grade approaches, before their infusion into patients with cancer. Herein, we discuss GMP-compliant strategies to isolate and expand human NK and CIK cells for immunotherapy purposes, focusing on clinical trials of adoptive transfer to patients with hematological malignancies.

Novel TLR7 agonist stimulates activity of CIK/NK immunological effector cells to enhance antitumor cytotoxicity

“…The killing rates were notably increased in the '+GD' and '+GD-IFN-γ' groups compared with the control group (P<0.05; effectors in immunotherapy (18). Culture systems used to provide adequate numbers of immune cells have focused primarily on stimulation with more effective cytokine and monoclonal antibodies (19,20).…”

A cross-sectional study of C-type lectin receptors (CD94 and CD314) in patients with HIV/AIDS and cancer

“…They are characterized by high expression of cytotoxic granules and perforins and lower cytokine secretion capacity [4]. The other subtype CD56bright is rare in the blood (± 10%) and constitutively express a greater number of cytokine receptors and chemokines and minor express amount of cytotoxic granules, generally showing a cytotoxic capacity lower than CD56dim subtype, but a superior ability to produce immunoregulatory cytokines [1][2][3][4].…”

“…Your functions are regulated through contact with the target cells and are controlled by the balance of the signals of activation and inhibitionreceived by thereceptors on the cell surface. The NK cell activity, however, is also modulated by accessory cells through dependent interactions contact and soluble factors such as IFNa, IL-12, IL-15 and IL-18 [2][3][4][5][6] These receptors compose distinct families of proteins: the Killer-cell immunoglobulin-like receptors (KIR), the natural cytotoxicity receptors (NCR) and the lectin-like domains. The latter is structurally characterized by anextracellular domains of C-type lectin, and is expressed as heterodimers composed of a common subunit (CD94) covalently bonded to a different chain encoded by a NKG2 family gene [7].…”

“…The NK cells are a subtype of the lymphocytes (comprising from 5 to 25% of the lymphocytes in the peripheral blood) capable of, when mature, induce a rapid response against tumor infected and abnormal cells without prior antigen exposure [1][2]. These cells reside primarily in the peripheral blood and bone marrow, but can be found in other locations such as secondary lymphoid organs [1].…”

“…These cells reside primarily in the peripheral blood and bone marrow, but can be found in other locations such as secondary lymphoid organs [1]. There are two phenotypically and functionally distinct subsets of NK cells that help protect against microbial infections and tumors, assisting the adaptive immune response [1][2][3]. These groups are divided based on the density of the CD56 expression.…”