Alphaviral vector-transduced dendritic cells are successful therapeutic vaccines against neu-overexpressing tumors in wild-type mice.
Vaccine
; 25(36): 6604-12, 2007 Sep 04.
Article
en En
| MEDLINE
| ID: mdl-17675184
ABSTRACT
While dendritic cell (DC) vaccines can protect hosts from tumor challenge, their ability to effectively inhibit the growth of established tumors remains indeterminate. Previously, we have shown that human DCs transduced with Venezuelan equine encephalitis virus replicon particles (VRPs) were potent stimulators of antigen-specific T cells in vitro. Therefore, we investigated the ability of VRP-transduced DCs (VRP-DCs) to induce therapeutic immunity in vivo against tumors overexpressing the neu oncoprotein. Transduction of murine DCs with VRPs resulted in high-level transgene expression, DC maturation and secretion of proinflammatory cytokines. Vaccination with VRP-DCs expressing a truncated neu oncoprotein induced robust neu-specific CD8(+) T cell and anti-neu IgG responses. Furthermore, a single vaccination with VRP-DCs induced the regression of large established tumors in wild-type mice. Interestingly, depletion of CD4(+), but not CD8(+), T cells completely abrogated inhibition of tumor growth following vaccination. Taken together, our results demonstrate that VRP-DC vaccines induce potent immunity against established tumors, and emphasize the importance of the generation of both CD4(+) T cell and B cell responses for efficient tumor inhibition. These findings provide the rationale for future evaluation of VRP-DC vaccines in the clinical setting.
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Células Dendríticas
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Vacunas contra el Cáncer
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Vectores Genéticos
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Neoplasias Experimentales
Límite:
Animals
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Female
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Humans
Idioma:
En
Revista:
Vaccine
Año:
2007
Tipo del documento:
Article
País de afiliación:
Estados Unidos