PMID- 26883680 OWN - NLM STAT- MEDLINE DCOM- 20170829 LR - 20180206 IS - 1521-7035 (Electronic) IS - 1521-6616 (Linking) VI - 177 DP - 2017 Apr TI - Natural killer cell adoptive immunotherapy: Coming of age. PG - 3-11 LID - S1521-6616(16)30019-5 [pii] LID - 10.1016/j.clim.2016.02.003 [doi] AB - Cell therapy is a promising alternative to harsh chemotherapy and radiation therapy for cancer. Natural killer (NK) cells in particular have great potential for direct use in adoptive immunotherapy (AI) for cancer and to improve the graft-vs-leukemia (GVL) effect of hematopoietic stem cell transplants (HSCTs). NK cell number and function are associated with a strong GVL effect without inducing graft-versus-host disease in most settings. Clinical trials demonstrating the therapeutic role of NK cells in HSCT recipients or testing the safety and efficacy of AI with NK cells have been primarily directed at treating acute myeloid leukemia, although investigators have used NK cells for treatment of other hematological diseases, sarcomas, carcinomas, and brain tumors. Major challenges must be overcome in making NK cell-based therapy cost-effective, the most important being the need to collect or generate an adequate number of effector cells. In this review, we discuss protocols for isolation, expansion, and in vitro propagation of large quantities of functional NK cells that meet the criteria for clinical applications. Among the methods described are the use of bioreactors for scaling up production and expansion of NK cells in the presence of interleukins and feeder cells. We also discuss novel methodologies that optimize the generation of clinical grade NK-cell products for AI. CI - Copyright (c) 2016 Elsevier Inc. All rights reserved. FAU - Baggio, Leticia AU - Baggio L AD - Universidade Federal do Rio Grande do Sul, Av. Paulo Gama, Porto Alegre, RS 91501-170, Brazil; Centro de Tecnologia e Terapia Celular, Hospital de Clinicas de Porto Alegre, R. Ramiro Barcelos, 2350, Porto Alegre, RS 90035-903, Brazil. FAU - Laureano, Alvaro Macedo AU - Laureano AM AD - Universidade Federal do Rio Grande do Sul, Av. Paulo Gama, Porto Alegre, RS 91501-170, Brazil; Centro de Tecnologia e Terapia Celular, Hospital de Clinicas de Porto Alegre, R. Ramiro Barcelos, 2350, Porto Alegre, RS 90035-903, Brazil. FAU - Silla, Lucia Mariano da Rocha AU - Silla LMDR AD - Universidade Federal do Rio Grande do Sul, Av. Paulo Gama, Porto Alegre, RS 91501-170, Brazil; Centro de Tecnologia e Terapia Celular, Hospital de Clinicas de Porto Alegre, R. Ramiro Barcelos, 2350, Porto Alegre, RS 90035-903, Brazil. FAU - Lee, Dean Anthony AU - Lee DA AD - Division of Pediatrics, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, United States; Immunology Program, The University of Texas Graduate School of Biomedical Sciences, 6767 Bertner Avenue, Houston, TX 77030, United States. Electronic address: dalee@mdanderson.org. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Review DEP - 20160214 PL - United States TA - Clin Immunol JT - Clinical immunology (Orlando, Fla.) JID - 100883537 SB - IM MH - Animals MH - Cell Transplantation MH - Humans MH - *Immunotherapy, Adoptive MH - Killer Cells, Natural/immunology/*transplantation MH - Lymphocyte Subsets OTO - NOTNLM OT - Acute myeloid leukemia OT - Adoptive immunotherapy OT - Ex vivo expansion OT - Graft versus leukemia OT - Graft-versus-host disease OT - Hematopoietic stem cell transplant OT - Natural killer cells EDAT- 2016/02/18 06:00 MHDA- 2017/08/30 06:00 CRDT- 2016/02/18 06:00 PHST- 2015/08/04 00:00 [received] PHST- 2016/02/06 00:00 [revised] PHST- 2016/02/09 00:00 [accepted] PHST- 2016/02/18 06:00 [pubmed] PHST- 2017/08/30 06:00 [medline] PHST- 2016/02/18 06:00 [entrez] AID - S1521-6616(16)30019-5 [pii] AID - 10.1016/j.clim.2016.02.003 [doi] PST - ppublish SO - Clin Immunol. 2017 Apr;177:3-11. doi: 10.1016/j.clim.2016.02.003. Epub 2016 Feb 14.