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Article: Human γδ T cells from G-CSF-mobilized donors retain strong tumoricidal activity and produce immunomodulatory cytokines after clinical-scale isolation

TitleHuman γδ T cells from G-CSF-mobilized donors retain strong tumoricidal activity and produce immunomodulatory cytokines after clinical-scale isolation
Authors
KeywordsCliniMACS
Transplantation
Immunotherapy
Killer cells
γδ T cells
Issue Date2005
Citation
Journal of Immunotherapy, 2005, v. 28, n. 1, p. 73-78 How to Cite?
AbstractHuman γδ T cells are a small fraction of T cells that have been shown to exert major histocompatibility (MHC)-unrestricted natural cytotoxicity against a variety of solid tumors and some subsets of leukemias and lymphomas. They are also involved in the immune response to certain bacterial, viral, and parasitic infections and expand significantly in CMV- or HSV-infected organ allografts. They are able to mediate antibody-dependent cytotoxicity and are not alloreactive, which makes them attractive candidates for cell-based immunotherapy. However, their frequency in peripheral blood is low and ex vivo expansion of γδ T cells is labor-extensive, does not always yield cells with full innate cytotoxic power, and has the potential for microbial contamination. Therefore, the authors developed a clinical-scale, automated cell purification method for the efficient enrichment of γδ T cells from leukapheresis products. Six leukapheresis products were purified for γδ T cells using a single-step immunomagnetic method. Purity and phenotype were assessed by flow cytometry. A standard Europium release assay was performed to determine the cytotoxic capacity of the cells. Cytokine production was measured using a multiplex sandwich immunoassay. The mean percentage of γδ T cells in the final product was 91%, with an average recovery of 63%. The cells showed a high co-expression of CD8, CD56, CD28, and CD11b/CD18. In some products an unusually high proportion of Vγ9Vδ1 T cells was found. The isolated cells were cytotoxic against the neuroblastoma cell line NB1691 and the erythroleukemic line K562 in vitro. They were able to produce a variety of immunomodulatory cytokines such as IFNγ, TNFα, and MIP-1β, but also GM-CSF and G-CSF when co-incubated in culture with and without various stimuli. In summary, the authors describe a rapid, automated, and efficient method for the large-scale enrichment of human γδ T cells. The cytotoxic properties of the cells were preserved. This method yields sufficient purified γδ T cells for use in adoptive immunotherapy as well as laboratory investigations and animal studies.
Persistent Identifierhttp://hdl.handle.net/10722/294401
ISSN
2020 Impact Factor: 4.456
2020 SCImago Journal Rankings: 1.805
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorOtto, Mario-
dc.contributor.authorBarfield, Raymond C.-
dc.contributor.authorIyengar, Rekha-
dc.contributor.authorGatewood, Janet-
dc.contributor.authorMüller, Ingo-
dc.contributor.authorHolladay, Martha S.-
dc.contributor.authorHouston, Jim-
dc.contributor.authorLeung, Wing-
dc.contributor.authorHandgretinger, Rupert-
dc.date.accessioned2020-12-03T08:22:39Z-
dc.date.available2020-12-03T08:22:39Z-
dc.date.issued2005-
dc.identifier.citationJournal of Immunotherapy, 2005, v. 28, n. 1, p. 73-78-
dc.identifier.issn1524-9557-
dc.identifier.urihttp://hdl.handle.net/10722/294401-
dc.description.abstractHuman γδ T cells are a small fraction of T cells that have been shown to exert major histocompatibility (MHC)-unrestricted natural cytotoxicity against a variety of solid tumors and some subsets of leukemias and lymphomas. They are also involved in the immune response to certain bacterial, viral, and parasitic infections and expand significantly in CMV- or HSV-infected organ allografts. They are able to mediate antibody-dependent cytotoxicity and are not alloreactive, which makes them attractive candidates for cell-based immunotherapy. However, their frequency in peripheral blood is low and ex vivo expansion of γδ T cells is labor-extensive, does not always yield cells with full innate cytotoxic power, and has the potential for microbial contamination. Therefore, the authors developed a clinical-scale, automated cell purification method for the efficient enrichment of γδ T cells from leukapheresis products. Six leukapheresis products were purified for γδ T cells using a single-step immunomagnetic method. Purity and phenotype were assessed by flow cytometry. A standard Europium release assay was performed to determine the cytotoxic capacity of the cells. Cytokine production was measured using a multiplex sandwich immunoassay. The mean percentage of γδ T cells in the final product was 91%, with an average recovery of 63%. The cells showed a high co-expression of CD8, CD56, CD28, and CD11b/CD18. In some products an unusually high proportion of Vγ9Vδ1 T cells was found. The isolated cells were cytotoxic against the neuroblastoma cell line NB1691 and the erythroleukemic line K562 in vitro. They were able to produce a variety of immunomodulatory cytokines such as IFNγ, TNFα, and MIP-1β, but also GM-CSF and G-CSF when co-incubated in culture with and without various stimuli. In summary, the authors describe a rapid, automated, and efficient method for the large-scale enrichment of human γδ T cells. The cytotoxic properties of the cells were preserved. This method yields sufficient purified γδ T cells for use in adoptive immunotherapy as well as laboratory investigations and animal studies.-
dc.languageeng-
dc.relation.ispartofJournal of Immunotherapy-
dc.subjectCliniMACS-
dc.subjectTransplantation-
dc.subjectImmunotherapy-
dc.subjectKiller cells-
dc.subjectγδ T cells-
dc.titleHuman γδ T cells from G-CSF-mobilized donors retain strong tumoricidal activity and produce immunomodulatory cytokines after clinical-scale isolation-
dc.typeArticle-
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1097/00002371-200501000-00009-
dc.identifier.pmid15614047-
dc.identifier.scopuseid_2-s2.0-11344259248-
dc.identifier.volume28-
dc.identifier.issue1-
dc.identifier.spage73-
dc.identifier.epage78-
dc.identifier.isiWOS:000226087300009-
dc.identifier.issnl1524-9557-

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