Inducing tolerance to a soluble foreign antigen by encapsulated cell transplants.
Mol Ther
; 13(2): 447-56, 2006 Feb.
Article
en En
| MEDLINE
| ID: mdl-16209937
ABSTRACT
The immune response to soluble antigens constitutes a current clinical problem impeding the development of protein therapeutics. We have developed an encapsulated-cell delivery system, which, transiently combined with an anti-CD154 antibody treatment, allows for the suppression of this immune response and the establishment of long-term secretion of a foreign antigen, human erythropoietin (huEPO). The chronic presence of antigen appears to be required to maintain this tolerance, as a 21-day gap in the exposure to huEPO is sufficient to restore the ability of mice to mount an antibody response. In contrast, chronic huEPO expression maintains tolerance even in the absence of further anti-CD154 treatment. These results suggest that a soluble antigenic protein can be continuously released, without inducing an antibody response, using encapsulated allogeneic cells. The temporary anti-CD154 treatment induces immune unresponsiveness to the delivered antigen, while the immunoprotected cell implant allows for chronic antigen release, favoring the establishment of tolerance.
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Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Mioblastos
/
Tolerancia Inmunológica
/
Antígenos
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Mol Ther
Asunto de la revista:
BIOLOGIA MOLECULAR
/
TERAPEUTICA
Año:
2006
Tipo del documento:
Article
País de afiliación:
Suiza