Potent immunotherapy against well-established thymoma using adoptively transferred transgene IL-6-engineered dendritic cell-stimulated CD8+ T-cells with prolonged survival and enhanced cytotoxicity.
J Gene Med
; 17(8-9): 153-60, 2015.
Article
en En
| MEDLINE
| ID: mdl-26212685
ABSTRACT
BACKGROUND:
Adoptive transfer of CD8(+) T-cells specific for tumor-antigens is an attractive strategy for anti-tumor therapy. In the present study, the subsets TA and TB were used to represent the population of CD8(+) T cells generated by culturing the respective cells with irradiated dendritic cells (DCs) pulsed with ovalbumin (OVA) protein and transfected with adenoviral vector constructs as described.METHODS:
Naïve OVA specific CD8(+) T cells were isolated from the spleen of OVA-specific T-cell receptor transgenic OTI mice. The subsets TA and TB were then generated by in vitro activating the population of CD8(+) T cells with OVA-pulsed DCs transfected with IL-6-expressing adenoviral vector (AdVIL-6 ) or the control vector (AdVNull ). To assess their in vivo immunotherapeutic effects, TA - or TB -cells were intravenously transferred into C57BL/6 mice bearing EG7 thymoma (6-8 mm in diameter).RESULTS:
TA -cells displayed a higher level of expression of CD62 l, IL-7R, FasL, perforin and CCR6, and also exhibited more potent in vitro cytotoxicity to OVA-expressing EG7 thymoma cells via perforin- and Fas/FasL-mediated apoptosis than TB -cells. CD8(+) T-cell survival was kinetically analyzed in C57BL/6 mice transferred with TA - or TB -cells by flow cytometry. We found that the adoptively transferred TA -cells had prolonged survival and enhanced T-cell memory development compared to TB -cells. In addition, TA -, but not TB -cells were able to eradicate well-established EG7 thymomas in all eight tumor-bearing mice.CONCLUSIONS:
Our data suggest that AdVIL-6 -transfected DC-stimulated CD8(+) T cells with potent cytotoxicity and survival advantage may serve as an effective adoptive CD8(+) T-cell immunotherapy strategy for anti-tumor treatment.Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Timoma
/
Células Dendríticas
/
Inmunoterapia Adoptiva
/
Interleucina-6
/
Linfocitos T CD8-positivos
/
Citotoxicidad Inmunológica
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
J Gene Med
Asunto de la revista:
BIOLOGIA MOLECULAR
/
GENETICA MEDICA
Año:
2015
Tipo del documento:
Article
País de afiliación:
Canadá