Stimulating surface molecules, Th1-polarizing cytokines, proven trafficking--a new protocol for the generation of clinical-grade dendritic cells.
Cytotherapy
; 15(4): 492-506, 2013 Apr.
Article
en En
| MEDLINE
| ID: mdl-23480952
ABSTRACT
BACKGROUND AIMS:
Dendritic cells (DC) have been vigorously investigated as an immunological basis for therapeutic vaccination against cancer and infections, even among patients after allogeneic stem cell transplantation.METHODS:
Effective induction of cell-mediated immunity strongly depends on the ability of DC to (i) migrate to the draining lymphoid organs mediated by chemokine receptors, (ii) prime T cells through high expression of costimulatory molecules and major histocompatibility complexes and (iii) secret Th1-polarizing cytokines such as Interleukin-12 (IL-12). However, there is no protocol to generate fully matured and functional DC according to methodical requirements of current good manufacturing practice (CGMP) guidelines.RESULTS:
We established a protocol conforming to CGMP standards that permits the generation of fully matured and functional DC on the basis of cell culture in adherence bags with the use of serum-free media with a maturation cocktail, containing tumor necrosis factor-alpha/Interferon-alpha/polyinosinicpolycytidylic acid. Our DC superiorly display three critical features for an effective induction of cell-mediated immunity without evidence of exhaustion, along with its ability to prime infectious or tumor-specific T cells in a short-term cell culture.CONCLUSIONS:
Our newly developed protocol offers an attractive method to produce fully matured Th1-polarizing DC with proven migratory and stimulatory capacity for any clinical application according to CGMP standards.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Células Dendríticas
/
Activación de Linfocitos
/
Células TH1
Tipo de estudio:
Guideline
Límite:
Humans
Idioma:
En
Revista:
Cytotherapy
Asunto de la revista:
TERAPEUTICA
Año:
2013
Tipo del documento:
Article
País de afiliación:
Alemania