Prevention of graft-versus-host-disease with preserved graft-versus-leukemia-effect by ex vivo and in vivo modulation of CD4(+) T-cells.
Cell Mol Life Sci
; 71(11): 2135-48, 2014 Jun.
Article
em En
| MEDLINE
| ID: mdl-24067988
ABSTRACT
This is the first report showing that an epitope-specific ex vivo modulation of an allogeneic hematopoietic stem cell graft by the anti-human CD4 antibody MAX.16H5 IgG1 simultaneously facilitates the anti-tumor capacity of the graft (Graft-versus-leukemia effect, GvL) and the long-term suppression of the deleterious side effect Graft-versus-host-disease (GvHD). To distinguish and consolidate GvL from GvHD, the anti-human CD4 antibody MAX16.H5 IgG1 was tested in murine GvHD and tumor models. The survival rate was significantly increased in recipients receiving a MAX.16H5 IgG1 short-term (2 h) pre-incubated graft even when tumor cells were co-transplanted or when recipient mice were treated by MAX.16H5 IgG1 before transplantation. After engraftment, regulatory T-cells are generated only supporting the GvL effect. It was also possible to transfer the immune tolerance from GvHD-free recipient chimeras into third party recipient mice without the need of reapplication of MAX.16H5 IgG1 anti-human CD4 antibodies. These findings are also benefical for patients with leukemia when no matched related or unrelated donor is available and provides a safer allogeneic HSCT, which is more effective against leukemia. It also facilitates allogeneic (stem) cell transplantations for other indications (e.g., autoimmune-disorders).
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Imunoglobulina G
/
Células-Tronco Hematopoéticas
/
Leucemia
/
Transplante de Células-Tronco Hematopoéticas
/
Efeito Enxerto vs Leucemia
/
Doença Enxerto-Hospedeiro
/
Soro Antilinfocitário
Idioma:
En
Ano de publicação:
2014
Tipo de documento:
Article