title: Improving efficacy of cancer immunotherapy by genetic modification of natural killer cells.
abstract: Natural killer (NK) cells are members of the innate immune system that recognize target cells via activating and inhibitory signals received through cell receptors. Derived from the lymphoid lineage, NK cells are able to produce cytokines and exert a cytotoxic effect on viral infected and malignant cells. It is their unique ability to lyse target cells rapidly and without prior education that renders NK cells a promising effector cell for adoptive cell therapy. However, both viruses and tumors employ evasion strategies to avoid attack by NK cells, which represent biological challenges that need to be harnessed to fully exploit the cytolytic potential of NK cells. Using genetic modification, the function of NK cells can be enhanced to improve their homing, cytolytic activity, in vivo persistence and safety. Examples include gene modification to express chemokine, high-affinity Fc receptor and chimeric antigen receptors, suicide genes and the forced expression of cytokines such as interleukin (IL)-2 and IL-15. Preclinical studies have clearly demonstrated that such approaches are effective in improving NK-cell function, homing and safety. In this review, we summarize the recent advances in the genetic manipulations of NK cells and their application for cellular immunotherapeutic strategies.
authors.affiliation: Institute for Biomedical Sciences, The George Washington University, Washington, DC, USA; Children's National Health System, Washington, DC, USA.
authors.forename: Rachel A
authors.initials: RA
authors.lastname: Burga
authors.affiliation: The University of Texas, MD Anderson Cancer Center, Houston, Texas, USA.
authors.forename: Tuongvan
authors.initials: T
authors.lastname: Nguyen
authors.affiliation: The University of Texas, MD Anderson Cancer Center, Houston, Texas, USA.
authors.forename: Jane
authors.initials: J
authors.lastname: Zulovich
authors.affiliation: The University of Texas, MD Anderson Cancer Center, Houston, Texas, USA.
authors.forename: Sarah
authors.initials: S
authors.lastname: Madonna
authors.affiliation: The University of Texas, MD Anderson Cancer Center, Houston, Texas, USA.
authors.forename: Loyda
authors.initials: L
authors.lastname: Ylisastigui
authors.affiliation: Institute for Biomedical Sciences, The George Washington University, Washington, DC, USA; Children's National Health System, Washington, DC, USA.
authors.forename: Rohan
authors.initials: R
authors.lastname: Fernandes
authors.affiliation: The University of Texas, MD Anderson Cancer Center, Houston, Texas, USA. Electronic address: ESYvon@mdanderson.org.
authors.forename: Eric
authors.initials: E
authors.lastname: Yvon
mesh_terms: D000818:Animals; D005818:Genetic Engineering; D006801:Humans; D057131:Immune Evasion; D016219:Immunotherapy, Adoptive / Q000379:methods*; D007694:Killer Cells, Natural / Q000276:immunology*; D009369:Neoplasms / Q000276:immunology* / Q000628:therapy*; D016896:Treatment Outcome
keywords: gene transfer; immunotherapy; natural killer cells