Induction of antitumor immunity with modified autologous cells expressing membrane-bound murine cytokines.
J Interferon Cytokine Res
; 19(12): 1391-401, 1999 Dec.
Article
em En
| MEDLINE
| ID: mdl-10638708
ABSTRACT
Development of cytokine gene-modified autologous tumor vaccines must take into account the strictly paracrine physiology of cytokines whose expression at the tumor microenvironment is important for the successful induction of tumor-specific immunity. In this study, we investigated the efficacy of a tumor vaccine composed of inactivated autologous cells transfected with two plasmid vectors encoding a mutant membrane-bound murine granulocyte-macrophage colony-stimulating factor (MuGM-CSF) and murine interferon-gamma (MuIFN-gamma). Expression of both cytokines as cell surface ligands on the highly metastatic D122 clone of Lewis lung carcinoma led to abrogation of their tumorigenicity and metastatic phenotype. More importantly, vaccination with irradiated tumor cells expressing the membrane-bound GM-CSF and IFN-gamma induced a cytotoxic T lymphocyte (CTL) response that protected syngeneic mice against a subsequent challenge with D122 cells as a primary tumor in preimmunized mice as well as against lung metastasis developing after surgical removal of the primary tumor in naive mice. Autologous cells expressing the membrane-bound GM-CSF and IFN-gamma exhibited comparable efficacy as an antimetastatic vaccine to a vaccine composed of transfectants expressing wild-type secreted cytokine molecules. These results indicate that membrane-bound cytokines can cause enhanced immunogenicity when transfected into tumor cells for the induction of antitumor immunity.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Citocinas
/
Vacinas Anticâncer
Limite:
Animals
Idioma:
En
Revista:
J Interferon Cytokine Res
Assunto da revista:
ALERGIA E IMUNOLOGIA
Ano de publicação:
1999
Tipo de documento:
Article
País de afiliação:
Israel