Recombinant adenovirus-transduced dendritic cell immunization in a murine model of central nervous system tumor.
Neurosurg Focus
; 9(6): e6, 2000 Dec 15.
Article
en En
| MEDLINE
| ID: mdl-16817689
ABSTRACT
OBJECT Dendritic cells (DCs) are potent antigen-presenting cells that have been shown to play a critical role in the initiation of host immune responses against tumor antigens. In this study, a recombinant adenovirus vector encoding the melanoma-associated antigen, MART-1, was used to transduce murine DCs, which were then tested for their ability to activate cytotoxic T lymphocytes (CTLs) and induce protective immunity against B16 melanoma tumor cells implanted intracranially. METHODS:
Genetic modification of murine bone marrow-derived DCs to express MART-1 was achieved through the use of an E1-deficient, recombinant adenovirus vector (AdVMART1). Sixty-two C57BL/6 mice were immunized by subcutaneous injection of AdVMART-1-transduced DCs (23 mice), untransduced DCs (17 mice), or sterile saline (22 mice). Using the B16 murine melanoma, which naturally expresses the MART-1 antigen, all the mice were then challenged intracranially with viable, unmodified syngeneic B16 tumor cells 7 days later. Splenocytes obtained from representative animals in each group were harvested for standard cytotoxicity and enzyme-linked immunospot assays. The remaining mice were followed for survival. Immunization of C57BL/6 mice with DCs transduced with AdVMART1-DC elicited the development of antigenspecific CTL responses. As evidenced by a prolonged survival curve when compared with control-immunized mice harboring intracranial B16 tumors, AdMART1-DC vaccination was able to elicit partial protection against central nervous system (CNS) tumor challenge in vivo. However, this CNS antitumor immunity was weaker than that previously demonstrated against subcutaneous B16 tumors in which the same vaccination strategy was used.CONCLUSIONS:
These data suggest that immune responses generated against CNS tumors by DC-based vaccines may be different from those obtained against subcutaneous tumors.
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Colección:
01-internacional
Base de datos:
MEDLINE
Contexto en salud:
2_ODS3
Problema de salud:
2_enfermedades_transmissibles
Asunto principal:
Células Dendríticas
/
Neoplasias Encefálicas
/
Modelos Animales de Enfermedad
/
Melanoma
/
Ratones Endogámicos C57BL
Límite:
Animals
/
Female
/
Humans
Idioma:
En
Revista:
Neurosurg Focus
Asunto de la revista:
NEUROCIRURGIA
Año:
2000
Tipo del documento:
Article
País de afiliación:
Estados Unidos