Way to go to exploit NK cells' versatile talents for cancer immunotherapy

which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. Natural killer (NK) cells are derived from CD34＋ hematopoietic progenitor cells. NK cells are lymphocytes of the innate immune system that function as both cytotoxic effectors and immunoregulatory cells secreting cytokines and chemokines. However, considerable experimental evidence suggests that NK cells, like T and B cells, have a certain feature of the adaptive immune system, i.e., memory. It has been reported that NK cells can directly kill target cells via the perforin−granzyme pathway, death receptor ligand-induced apoptosis, and antibody-dependent cellular cytotoxicity (ADCC). Owing to these abilities, NK cells have been examined clinically in several immunotherapeutic strategies for cancer. Two general approaches for NK cell-based immunotherapy for cancer have been developed. The first approach involves in vivo activation and expansion of NK cells in patients with cancer by administering cytokines such as interleukin (IL)-2. The second approach involves the infusion of ex vivo manipulated NK cells (autologous or allogeneic NK cells, purified or expanded NK cells) into patients with cancer. Recently, in addition to these approaches, administration of a tumor antigen (TA)-specific monoclonal antibody (mAb) (e.g. rituximab) into patients with TA-expressing cancers has been performed , whereby the Fc portion of the antibody can bind to CD16 expressed on NK cells, thus initiating ADCC [1]. To enable successful adoptive cell therapy, several methods for generating a large number of activated NK cells have been introduced. Although several groups tried to expand NK cells using OKT-3 anti-CD3 antibody without feeder cells, remarkable NK cell-expansion rates (30– 31,747-fold within 7–21 d) were achieved when feeder cells were used. Commonly used feeder cell lines for successful NK cell expansion were RPMI8866, Wilms tumor cell line (HFWT), Epstein-Barr lymphoblastoid cell line (EBV-LCL), Jurkat (designated as KL-1 from Korean Cell Line Bank), K562, and genetically engineered K562 cells (i.e., K562-mb15-41BBL and K562-cl9-mIL21) [2-5]. In addition to these cancer cell lines, allogeneic peripheral blood mononuclear cells (PBMCs) can also be used to activate and expand NK cells. So far, however, the comparison of the feeder activities between feeder cells and the mechanism of the feeder cells have not been well studied. In the current issue of Blood Research, Bae et al. report the development of NK cell expansion methods by using K562 feeder cells [6]. They compared feeder activities of three different cells−PBMCs, Jurkat, and K562. The results showed …