title: mRNA Transfection to Improve NK Cell Homing to Tumors.
abstract: The ability of natural killer (NK) cells to mediate antitumor effects following adoptive transfer is dependent on their capacity to traffic to the microenvironment where tumors reside. Recent studies have shown that cytokine-activated and ex vivo-expanded NK cells lack or express at low levels homing receptors required to achieve tissue-specific tumor targeting by cells administered intravenously. In this chapter, we describe a method to enhance NK cell homing toward specific chemoattractants expressed in secondary lymphoid tissues through genetic modification of NK cells using mRNA electroporation. The method described here is scalable, cGMP-compliant, and offers a strategy to bolster the efficacy of adoptive NK cell immunotherapy for the treatment of hematological malignancies in the clinic.
authors.affiliation: Laboratory of Transplantation Immunotherapy, Hematology Branch, National Heart Lung and Blood Institute, National Institutes of Health, Building 10-CRC Room 3-5330, Bethesda, MD, 20814, USA.|Institute of Biomedical Sciences, George Washington University, Washington DC, 20037, USA.
authors.forename: Emily R
authors.initials: ER
authors.lastname: Levy
authors.affiliation: Laboratory of Transplantation Immunotherapy, Hematology Branch, National Heart Lung and Blood Institute, National Institutes of Health, Building 10-CRC Room 3-5330, Bethesda, MD, 20814, USA.
authors.forename: Mattias
authors.initials: M
authors.lastname: Carlsten
authors.affiliation: Laboratory of Transplantation Immunotherapy, Hematology Branch, National Heart Lung and Blood Institute, National Institutes of Health, Building 10-CRC Room 3-5330, Bethesda, MD, 20814, USA. childsr@nhlbi.nih.gov.
authors.forename: Richard W
authors.initials: RW
authors.lastname: Childs
mesh_terms: D045744:Cell Line, Tumor; D002465:Cell Movement; D002478:Cells, Cultured; D018920:Coculture Techniques; D016207:Cytokines / Q000378:metabolism; D018274:Electroporation; D006801:Humans; D016219:Immunotherapy, Adoptive; D007694:Killer Cells, Natural / Q000166:cytology*; D009369:Neoplasms / Q000276:immunology* / Q000628:therapy; D009928:Organ Specificity; D012333:RNA, Messenger / Q000235:genetics*; D054400:Receptors, CCR7 / Q000235:genetics; D014162:Transfection / Q000379:methods*
chemical_list: C515370:CCR7 protein, human; D016207:Cytokines; D012333:RNA, Messenger; D054400:Receptors, CCR7
keywords: Cellular immunotherapy; Chemotaxis; Electroporation; Lymph node homing; Natural killer cells