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Article: Combination immunotherapy with clinical-scale enriched human γδ T cells, hu14.18 antibody, and the immunocytokine Fc-IL7 in disseminated neuroblastoma

TitleCombination immunotherapy with clinical-scale enriched human γδ T cells, hu14.18 antibody, and the immunocytokine Fc-IL7 in disseminated neuroblastoma
Authors
Issue Date2005
Citation
Clinical Cancer Research, 2005, v. 11, n. 23, p. 8486-8491 How to Cite?
AbstractPurpose: To evaluate a combined cellular and humoral immunotherapy regimen in a mouse model of disseminated human neuroblastoma. We tested combinations of clinical-grade, isolated human γδ T cells with the humanized anti-GD2 antibody hu14.18 and a novel fusion cytokine, Fc-IL7. Experimental Design: γδ T cells were large-scale enriched from leukapheresis product obtained from granulocyte colony-stimulating factor-mobilized donors. γδ T cell cytotoxicity was tested in a europium-TDA release assay. The effect of Fc-IL7 on γδ T-cell survival in vitro was assessed by flow cytometry. NOD.CB17-Prkdcscid/J mice received 1 × 10 6 NB-1691 neuroblastoma cells via the tail vein 5 to 6 days before therapy began. Treatment, for five consecutive weeks, consisted of injections of 1 × 106 γδ T cells weekly, 1 × 10 6 γδ T cells weekly, and 20 μg hu14.18 antibody four times per week, or 1 × 106 γδ T cells weekly with 20 μg hu14.18 antibody four times per week, and 20 μg Fc-IL7 once weekly. Results: The natural cytotoxicity of γδ T cells to NB-1691 cells in vitro was dramatically enhanced by hu14.18 antibody. Fc-IL7 effectively kept cultured γδ T cells viable. Combination therapy with γδ T cells and hu14.18 antibody significantly enhanced survival (P = 0.001), as did treatment with γδ T cells, hu14.18 antibody, and Fc-IL7 (P = 0.005). Inclusion of Fc-IL7 offered an additional survival benefit (P = 0.04). Conclusions: We have shown a new and promising immunotherapy regimen for neuroblastoma that requires clinical evaluation. Our approach might also serve as a therapeutic model for other malignancies. © 2005 American Association for Cancer Research.
Persistent Identifierhttp://hdl.handle.net/10722/294410
ISSN
2020 Impact Factor: 12.531
2020 SCImago Journal Rankings: 5.427
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorOtto, Mario-
dc.contributor.authorBarfield, Raymond C.-
dc.contributor.authorMartin, William J.-
dc.contributor.authorIyengar, Rekha-
dc.contributor.authorLeung, Wing-
dc.contributor.authorLeimig, Thasia-
dc.contributor.authorChaleff, Stanley-
dc.contributor.authorGillies, Stephen D.-
dc.contributor.authorHandgretinger, Rupert-
dc.date.accessioned2020-12-03T08:22:40Z-
dc.date.available2020-12-03T08:22:40Z-
dc.date.issued2005-
dc.identifier.citationClinical Cancer Research, 2005, v. 11, n. 23, p. 8486-8491-
dc.identifier.issn1078-0432-
dc.identifier.urihttp://hdl.handle.net/10722/294410-
dc.description.abstractPurpose: To evaluate a combined cellular and humoral immunotherapy regimen in a mouse model of disseminated human neuroblastoma. We tested combinations of clinical-grade, isolated human γδ T cells with the humanized anti-GD2 antibody hu14.18 and a novel fusion cytokine, Fc-IL7. Experimental Design: γδ T cells were large-scale enriched from leukapheresis product obtained from granulocyte colony-stimulating factor-mobilized donors. γδ T cell cytotoxicity was tested in a europium-TDA release assay. The effect of Fc-IL7 on γδ T-cell survival in vitro was assessed by flow cytometry. NOD.CB17-Prkdcscid/J mice received 1 × 10 6 NB-1691 neuroblastoma cells via the tail vein 5 to 6 days before therapy began. Treatment, for five consecutive weeks, consisted of injections of 1 × 106 γδ T cells weekly, 1 × 10 6 γδ T cells weekly, and 20 μg hu14.18 antibody four times per week, or 1 × 106 γδ T cells weekly with 20 μg hu14.18 antibody four times per week, and 20 μg Fc-IL7 once weekly. Results: The natural cytotoxicity of γδ T cells to NB-1691 cells in vitro was dramatically enhanced by hu14.18 antibody. Fc-IL7 effectively kept cultured γδ T cells viable. Combination therapy with γδ T cells and hu14.18 antibody significantly enhanced survival (P = 0.001), as did treatment with γδ T cells, hu14.18 antibody, and Fc-IL7 (P = 0.005). Inclusion of Fc-IL7 offered an additional survival benefit (P = 0.04). Conclusions: We have shown a new and promising immunotherapy regimen for neuroblastoma that requires clinical evaluation. Our approach might also serve as a therapeutic model for other malignancies. © 2005 American Association for Cancer Research.-
dc.languageeng-
dc.relation.ispartofClinical Cancer Research-
dc.titleCombination immunotherapy with clinical-scale enriched human γδ T cells, hu14.18 antibody, and the immunocytokine Fc-IL7 in disseminated neuroblastoma-
dc.typeArticle-
dc.description.naturelink_to_OA_fulltext-
dc.identifier.doi10.1158/1078-0432.CCR-05-1184-
dc.identifier.pmid16322312-
dc.identifier.scopuseid_2-s2.0-28544448891-
dc.identifier.volume11-
dc.identifier.issue23-
dc.identifier.spage8486-
dc.identifier.epage8491-
dc.identifier.isiWOS:000233701300036-
dc.identifier.issnl1078-0432-

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