Expansion of allogeneic NK cells with efficient antibody-dependent cell cytotoxicity against multiple tumors
Resumen: Monoclonal antibodies (mAbs) have significantly improved the treatment of certain cancers. However, in general mAbs alone have limited therapeutic activity. One of their main mechanisms of action is to induce antibody-dependent cell-mediated cytotoxicity (ADCC), which is mediated by natural killer (NK) cells. Unfortunately, most cancer patients have severe immune dysfunctions affecting NK activity. This can be circumvented by the injection of allogeneic, expanded NK cells, which is safe. Nevertheless, despite their strong cytolytic potential against different tumors, clinical results have been poor. Methods: We combined allogeneic NK cells and mAbs to improve cancer treatment. We generated expanded NK cells (e-NK) with strong in vitro and in vivo ADCC responses against different tumors and using different therapeutic mAbs, namely rituximab, obinutuzumab, daratumumab, cetuximab and trastuzumab. Results: Remarkably, e-NK cells can be stored frozen and, after thawing, armed with mAbs. They mediate ADCC through degranulation-dependent and -independent mechanisms. Furthermore, they overcome certain anti-apoptotic mechanisms found in leukemic cells. Conclusion: We have established a new protocol for activation/expansion of NK cells with high ADCC activity. The use of mAbs in combination with e-NK cells could potentially improve cancer treatment.
Idioma: Inglés
DOI: 10.7150/thno.25149
Año: 2018
Publicado en: THERANOSTICS 8, 14 (2018), 3856-3869
ISSN: 1838-7640

Factor impacto JCR: 8.063 (2018)
Categ. JCR: MEDICINE, RESEARCH & EXPERIMENTAL rank: 10 / 135 = 0.074 (2018) - Q1 - T1
Factor impacto SCIMAGO: 2.176 - Pharmacology, Toxicology and Pharmaceutics (miscellaneous) (Q1) - Medicine (miscellaneous) (Q1)

Financiación: info:eu-repo/grantAgreement/ES/MINECO/SAF2014-54763-C2-1-R
Financiación: info:eu-repo/grantAgreement/ES/MINECO/SAF2014-54763-C2-2-R
Financiación: info:eu-repo/grantAgreement/ES/MINECO/SAF2017-83120-C2-1-R
Tipo y forma: Article (Published version)
Área (Departamento): Área Inmunología (Dpto. Microb.Med.Pr.,Sal.Públ.)
Área (Departamento): Área Bioquímica y Biolog.Mole. (Dpto. Bioq.Biolog.Mol. Celular)


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Articles > Artículos por área > Bioquímica y Biología Molecular
Articles > Artículos por área > Inmunología



 Record created 2018-09-21, last modified 2020-01-17


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