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Article: A clinically adaptable method to enhance the cytotoxicity of natural killer cells against B-cell malignancies

TitleA clinically adaptable method to enhance the cytotoxicity of natural killer cells against B-cell malignancies
Authors
KeywordsNon-Hodgkin lymphoma
Cell therapy
Natural killer cells
Acute lymphoblastic leukemia
Issue Date2012
Citation
Cytotherapy, 2012, v. 14, n. 7, p. 830-840 How to Cite?
AbstractBackground aims. Retroviral transduction of anti-CD19 chimeric antigen receptors significantly enhances the cytotoxicity of natural killer (NK) cells against B-cell malignancies. We aimed to validate a more practical, affordable and safe method for this purpose. Methods. We tested the expression of a receptor containing CD3ζ and 4-1BB signaling molecules (anti-CD19-BB- ζ) in human NK cells after electroporation with the corresponding mRNA using a clinical-grade electroporator. The cytotoxic capacity of the transfected NK cells was tested in vitro and in a mouse model of leukemia. Results. Median anti-CD19-BB-ζ expression 24 h after electroporation was 40.3% in freshly purified (n = 18) and 61.3% in expanded (n = 31) NK cells; median cell viability was 90%. NK cells expressing anti-CD19-BB-ζ secreted interferon (IFN)-γ in response to CD19-positive target cells and had increased cytotoxicity. Receptor expression was detectable 6 h after electroporation, reaching maximum levels at 24-48 h; specific anti-CD19 cytotoxicity was observed at 96 h. Levels of expression and cytotoxicities were comparable with those achieved by retroviral transduction. A large-scale protocol was developed and applied to expanded NK cells (median NK cell number 2.5 × 108, n = 12). Median receptor expression after 24 h was 82.0%; NK cells transfected under these conditions exerted considerable cytotoxicity in xenograft models of B-cell leukemia. Conclusions. The method described here represents a practical way to augment the cytotoxicity of NK cells against B-cell malignancies. It has the potential to be extended to other targets beyond CD19 and should facilitate the clinical use of redirected NK cells for cancer therapy. © 2012 Informa Healthcare.
Persistent Identifierhttp://hdl.handle.net/10722/294453
ISSN
2023 Impact Factor: 3.7
2023 SCImago Journal Rankings: 1.084
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorShimasaki, Noriko-
dc.contributor.authorFujisaki, Hiroyuki-
dc.contributor.authorCho, Duck-
dc.contributor.authorMasselli, Marika-
dc.contributor.authorLockey, Timothy-
dc.contributor.authorEldridge, Paul-
dc.contributor.authorLeung, Wing-
dc.contributor.authorCampana, Dario-
dc.date.accessioned2020-12-03T08:22:46Z-
dc.date.available2020-12-03T08:22:46Z-
dc.date.issued2012-
dc.identifier.citationCytotherapy, 2012, v. 14, n. 7, p. 830-840-
dc.identifier.issn1465-3249-
dc.identifier.urihttp://hdl.handle.net/10722/294453-
dc.description.abstractBackground aims. Retroviral transduction of anti-CD19 chimeric antigen receptors significantly enhances the cytotoxicity of natural killer (NK) cells against B-cell malignancies. We aimed to validate a more practical, affordable and safe method for this purpose. Methods. We tested the expression of a receptor containing CD3ζ and 4-1BB signaling molecules (anti-CD19-BB- ζ) in human NK cells after electroporation with the corresponding mRNA using a clinical-grade electroporator. The cytotoxic capacity of the transfected NK cells was tested in vitro and in a mouse model of leukemia. Results. Median anti-CD19-BB-ζ expression 24 h after electroporation was 40.3% in freshly purified (n = 18) and 61.3% in expanded (n = 31) NK cells; median cell viability was 90%. NK cells expressing anti-CD19-BB-ζ secreted interferon (IFN)-γ in response to CD19-positive target cells and had increased cytotoxicity. Receptor expression was detectable 6 h after electroporation, reaching maximum levels at 24-48 h; specific anti-CD19 cytotoxicity was observed at 96 h. Levels of expression and cytotoxicities were comparable with those achieved by retroviral transduction. A large-scale protocol was developed and applied to expanded NK cells (median NK cell number 2.5 × 108, n = 12). Median receptor expression after 24 h was 82.0%; NK cells transfected under these conditions exerted considerable cytotoxicity in xenograft models of B-cell leukemia. Conclusions. The method described here represents a practical way to augment the cytotoxicity of NK cells against B-cell malignancies. It has the potential to be extended to other targets beyond CD19 and should facilitate the clinical use of redirected NK cells for cancer therapy. © 2012 Informa Healthcare.-
dc.languageeng-
dc.relation.ispartofCytotherapy-
dc.subjectNon-Hodgkin lymphoma-
dc.subjectCell therapy-
dc.subjectNatural killer cells-
dc.subjectAcute lymphoblastic leukemia-
dc.titleA clinically adaptable method to enhance the cytotoxicity of natural killer cells against B-cell malignancies-
dc.typeArticle-
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.3109/14653249.2012.671519-
dc.identifier.pmid22458956-
dc.identifier.scopuseid_2-s2.0-84863915982-
dc.identifier.volume14-
dc.identifier.issue7-
dc.identifier.spage830-
dc.identifier.epage840-
dc.identifier.eissn1477-2566-
dc.identifier.isiWOS:000306422700008-
dc.identifier.issnl1465-3249-

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