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Enhanced cytotoxicity of natural killer cells following the acquisition of chimeric antigen receptors through trogocytosis
- Source :
- PLoS ONE, Vol 9, Iss 10, p e109352 (2014), PLoS ONE
- Publication Year :
- 2014
- Publisher :
- Public Library of Science (PLoS), 2014.
-
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.
- Subjects :
- Cytotoxicity, Immunologic
Lymphoma, B-Cell
Trogocytosis
medicine.medical_treatment
Antigens, CD19
Immunology
lcsh:Medicine
Biology
Immunophenotyping
Viral vector
Interleukin 21
Medicine and Health Sciences
medicine
Humans
lcsh:Science
Cells, Cultured
Multidisciplinary
Lymphokine-activated killer cell
lcsh:R
Biology and Life Sciences
Hematology
Immunotherapy
Coculture Techniques
Chimeric antigen receptor
Cell biology
Killer Cells, Natural
Receptors, Antigen
Oncology
Interleukin 12
lcsh:Q
K562 Cells
Research Article
K562 cells
Subjects
Details
- Language :
- English
- ISSN :
- 19326203
- Volume :
- 9
- Issue :
- 10
- Database :
- OpenAIRE
- Journal :
- PLoS ONE
- Accession number :
- edsair.doi.dedup.....863af0adb22fefddc55e395ab29130e0