title: Enhanced cytotoxicity of natural killer cells following the acquisition of chimeric antigen receptors through trogocytosis.
abstract: Natural killer (NK) cells have the capacity to target tumors and are ideal candidates for immunotherapy. Viral vectors have been used to genetically modify in vitro expanded NK cells to express chimeric antigen receptors (CARs), which confer cytotoxicity against tumors. However, use of viral transduction methods raises the safety concern of viral integration into the NK cell genome. In this study, we used trogocytosis as a non-viral method to modify NK cells for immunotherapy. A K562 cell line expressing high levels of anti-CD19 CARs was generated as a donor cell to transfer the anti-CD19 CARs onto NK cells via trogocytosis. Anti-CD19 CAR expression was observed in expanded NK cells after these cells were co-cultured for one hour with freeze/thaw-treated donor cells expressing anti-CD19 CARs. Immunofluorescence analysis confirmed the localization of the anti-CD19 CARs on the NK cell surface. Acquisition of anti-CD19 CARs via trogocytosis enhanced NK cell-mediated cytotoxicity against the B-cell acute lymphoblastic leukemia (B-ALL) cell lines and primary B-ALL cells derived from patients. To our knowledge, this is the first report that describes the increased cytotoxicity of NK cells following the acquisition of CARs via trogocytosis. This novel strategy could be a potential valuable therapeutic approach for the treatment of B-cell tumors.
authors.affiliation: Department of Obstetrics and Gynecology, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan.
authors.forename: Fu-Nan
authors.initials: FN
authors.lastname: Cho
authors.affiliation: Department of Medical Education and Research, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan.
authors.forename: Tsung-Hsien
authors.initials: TH
authors.lastname: Chang
authors.affiliation: Department of Medical Education and Research, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan.
authors.forename: Chih-Wen
authors.initials: CW
authors.lastname: Shu
authors.affiliation: Department of Pediatrics, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan.
authors.forename: Ming-Chin
authors.initials: MC
authors.lastname: Ko
authors.affiliation: Graduate Institute of Cancer Biology and Drug Discovery and Center of Excellence for Cancer Research, Taipei Medical University, Taipei, Taiwan.
authors.forename: Shuen-Kuei
authors.initials: SK
authors.lastname: Liao
authors.affiliation: Department of Pediatrics, Children's Hospital and School of Chinese Medicine, China Medical University Hospitals, Taichung, Taiwan.
authors.forename: Kang-Hsi
authors.initials: KH
authors.lastname: Wu
authors.affiliation: Haematology-Oncology Section, Department of Medicine, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan.
authors.forename: Ming-Sun
authors.initials: MS
authors.lastname: Yu
authors.affiliation: Haematology-Oncology Section, Department of Medicine, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan.
authors.forename: Shyh-Jer
authors.initials: SJ
authors.lastname: Lin
authors.affiliation: Haematology-Oncology Section, Department of Medicine, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan.
authors.forename: Ying-Chung
authors.initials: YC
authors.lastname: Hong
authors.affiliation: Department of Radiation Oncology, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan.
authors.forename: Chien-Hsun
authors.initials: CH
authors.lastname: Chen
authors.affiliation: Department of Pediatrics, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan.
authors.forename: Chien-Hui
authors.initials: CH
authors.lastname: Hung
authors.affiliation: Department of Pediatrics, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan; Faculty of Medicine, National Yang-Ming University, Taipei, Taiwan; Department of Nursing, Tajen University, Yanpu Township, Pingtung County, Taiwan.
authors.forename: Yu-Hsiang
authors.initials: YH
authors.lastname: Chang
mesh_terms: D018941:Antigens, CD19 / Q000235:genetics / Q000378:metabolism; D002478:Cells, Cultured; D018920:Coculture Techniques; D003602:Cytotoxicity, Immunologic; D006801:Humans; D016130:Immunophenotyping; D020014:K562 Cells; D007694:Killer Cells, Natural / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D016393:Lymphoma, B-Cell / Q000378:metabolism / Q000473:pathology; D011946:Receptors, Antigen / Q000235:genetics / Q000378:metabolism*
chemical_list: D018941:Antigens, CD19; D011946:Receptors, Antigen