title: Natural killer cell engineering for cellular therapy of cancer.
abstract: Natural killer (NK) cells can kill transformed cells and represent a promising tool for the treatment of cancer. Their function is governed by a balance of stimulatory and inhibitory signals triggered by surface receptors. Advances in NK cell therapy require the development of dependable methods for obtaining an adequate number of effector cells; additional activation or genetic modification may further increase their anticancer capacity. A method for NK cell expansion used in our laboratory relies on a genetically modified form of the K562 myeloid leukemia cell line, engineered to express a membrane-bound form of interleukin-15 and the ligand for the costimulatory molecule 4-1BB (CD137). Expanded NK cells can be transduced with genes encoding chimeric antigen receptors that stimulate tumor cell-specific cytotoxicity. These methods for NK cell expansion and genetic modification have been adapted to large-scale, clinical-grade, Current Good Manufacturing Practice conditions and support two active clinical trials. Summarized are current efforts for NK cell immunotherapy for cancer and future perspectives.
authors.affiliation: Department of Oncology, St. Jude Children's Research Hospital, Memphis, TN, USA. david.shook@stjude.org
authors.forename: D R
authors.initials: DR
authors.lastname: Shook
authors.forename: D
authors.initials: D
authors.lastname: Campana
mesh_terms: D053330:4-1BB Ligand / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D060846:Cell Engineering / Q000379:methods*; D006801:Humans; D016219:Immunotherapy, Adoptive; D019409:Interleukin-15 / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D020014:K562 Cells; D007694:Killer Cells, Natural / Q000276:immunology* / Q000637:transplantation*; D009369:Neoplasms / Q000276:immunology / Q000378:metabolism / Q000628:therapy*
chemical_list: D053330:4-1BB Ligand; C569274:IL15 protein, human; D019409:Interleukin-15; C505974:TNFSF9 protein, human
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