title: Natural killer cell adoptive immunotherapy: Coming of age.
abstract: 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.
authors.affiliation: Universidade Federal do Rio Grande do Sul, Av. Paulo Gama, Porto Alegre, RS 91501-170, Brazil; Centro de Tecnologia e Terapia Celular, Hospital de Clínicas de Porto Alegre, R. Ramiro Barcelos, 2350, Porto Alegre, RS 90035-903, Brazil.
authors.forename: Letícia
authors.initials: L
authors.lastname: Baggio
authors.affiliation: Universidade Federal do Rio Grande do Sul, Av. Paulo Gama, Porto Alegre, RS 91501-170, Brazil; Centro de Tecnologia e Terapia Celular, Hospital de Clínicas de Porto Alegre, R. Ramiro Barcelos, 2350, Porto Alegre, RS 90035-903, Brazil.
authors.forename: Álvaro Macedo
authors.initials: ÁM
authors.lastname: Laureano
authors.affiliation: Universidade Federal do Rio Grande do Sul, Av. Paulo Gama, Porto Alegre, RS 91501-170, Brazil; Centro de Tecnologia e Terapia Celular, Hospital de Clínicas de Porto Alegre, R. Ramiro Barcelos, 2350, Porto Alegre, RS 90035-903, Brazil.
authors.forename: Lucia Mariano da Rocha
authors.initials: LMDR
authors.lastname: Silla
authors.affiliation: 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.
authors.forename: Dean Anthony
authors.initials: DA
authors.lastname: Lee
mesh_terms: D000818:Animals; D017690:Cell Transplantation; D006801:Humans; D016219:Immunotherapy, Adoptive; D007694:Killer Cells, Natural / Q000276:immunology / Q000637:transplantation*; D016131:Lymphocyte Subsets
keywords: Acute myeloid leukemia; Adoptive immunotherapy; Ex vivo expansion; Graft versus leukemia; Graft-versus-host disease; Hematopoietic stem cell transplant; Natural killer cells