Immunotherapy with liposome-bound TRAIL overcomes partial protection to soluble TRAIL-induced apoptosis offered by down-regulation of Bim in leukemic cells
Clin. transl. oncol. (Print)
; 17(8): 547-667, ago. 2015. ilus
Artigo
em Inglês
| IBECS
| ID: ibc-138181
Biblioteca responsável:
ES1.1
Localização: BNCS
ABSTRACT
Purpose. Human Apo2-Ligand/TRAIL secreted by natural killer cells and cytotoxic T lymphocytes plays an important role immunosurveillance controlling tumor growth and metastasis. Moreover, the fact that Apo2L/TRAIL is capable of inducing cell death in tumor cells but not in normal cells makes this death ligand a promising anti-tumor agent. Previous data from our group demonstrated that Apo2L/TRAIL was physiologically released as transmembrane protein inserted in lipid vesicles, called exosomes. Recently, we demonstrated that artificial lipid nanoparticles coated with bioactive Apo2L/TRAIL (LUV-TRAIL) resembling the natural exosomes, greatly improved Apo2L/TRAIL activity and were able to induce apoptosis in hematological malignancies. In this study, we have deepened in the underlying mechanism of action of LUV-TRAIL in hematologic cells. Methods/patients. Cytotoxic ability of LUV-TRAIL was assessed on Jurkat cells either over-expressing the anti-apoptotic protein Mcl1 or down-regulating the pro-apoptotic protein Bim previously generated in our laboratory. We also tested LUV-TRAIL cytotoxic ability against primary human leukemic cells from T-cell ALL patient. Results. Silencing Bim but not Mcl-1 over-expression partially protects Jurkat cells from apoptosis induced by sTRAIL. LUV-TRAIL induced caspase-8 and caspase-3 activation and killed Jurkat-Mcl1 and Jurkat-shBim more efficiently than sTRAIL independently of the mitochondrial pathway. On the other hand, LUV-TRAIL were clearly more cytotoxic against primary leukemic cells from a T-cell ALL patient than sTRAIL. Conclusion. Tethering Apo2L/TRAIL to the surface of lipid nanoparticles greatly increases its bioactivity and could be of potential use in anti-tumor therapeutics (AU)
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Coleções:
Bases de dados nacionais
/
Espanha
Contexto em Saúde:
ODS3 - Meta 3.4 Reduzir as mortes prematuras devido doenças não transmissíveis
Problema de saúde:
Leucemia
Base de dados:
IBECS
Assunto principal:
Testes Imunológicos de Citotoxicidade
/
Morte Celular
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Receptores do Fator de Necrose Tumoral
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Imunoterapia
/
Lipossomos
Limite:
Feminino
/
Humanos
/
Masculino
Idioma:
Inglês
Revista:
Clin. transl. oncol. (Print)
Ano de publicação:
2015
Tipo de documento:
Artigo
Instituição/País de afiliação:
Hospital Universitario Miguel Servet/Spain
/
Universidad de Zaragoza/Spain