RANTES secretion by gene-modified tumor cells results in loss of tumorigenicity in vivo: role of immune cell subpopulations.
Hum Gene Ther
; 7(13): 1545-53, 1996 Aug 20.
Article
em En
| MEDLINE
| ID: mdl-8864755
ABSTRACT
An immunogenic murine fibrosarcoma cell line was genetically modified to express and produce the human RANTES chemokine stably. In in vitro chemotaxis assays purified recombinant human RANTES as well as human RANTES secreted by the modified murine tumor cells were strongly chemoattractant for mouse CD8+ /Thy-1+ tumor-infiltrating lymphocytes (TIL). RANTES production did not alter the growth of these cytokine gene-modified tumor cells in vitro, but injection of RANTES-secreting cells resulted in the abolition of the ability of those cells to form solid tumors in vivo. The growth of tumors could be restored by co-administration of monoclonal antibodies that inhibit the function of various subsets of immune cells. For example, depletion of CD8+ T cells by antibody administration resulted in complete restoration of solid tumor formation by RANTES-secreting cells, whereas depletion of the CD4+ T cell population resulted in a partial restoration of tumor formation. Additionally, administration of an anti-CR3 monoclonal antibody known to inhibit the in vivo migration of macrophages also completely restored the tumorigenicity of RANTES-secreting fibrosarcoma cells. Thus, the human RANTES chemokine can abolish tumorigenicity of an immunogenic fibrosarcoma in an in vivo murine model, and this process is mediated by various subpopulations of immune effector cells.
Buscar no Google
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Técnicas de Transferência de Genes
/
Quimiocina CCL5
/
Neoplasias Experimentais
Tipo de estudo:
Prognostic_studies
Limite:
Animals
/
Female
/
Humans
Idioma:
En
Revista:
Hum Gene Ther
Assunto da revista:
GENETICA MEDICA
/
TERAPEUTICA
Ano de publicação:
1996
Tipo de documento:
Article
País de afiliação:
Estados Unidos