Retroviral transduction of human dendritic cells with a tumor-associated antigen gene.
Cancer Res
; 56(24): 5672-7, 1996 Dec 15.
Article
em En
| MEDLINE
| ID: mdl-8971174
ABSTRACT
Dendritic cells (DCs) are potent antigen-presenting cells that can activate quiescent T lymphocytes. When pulsed with tumor-associated antigen (TAA) peptide or protein, murine DCs can provide antitumor immunity. We reasoned that DCs retrovirally transduced with TAA genes might have important advantages over peptide- or protein-pulsed DCs, including long-term TAA presentation in vivo, and presentation of important but undefined epitopes. Therefore, we attempted to retrovirally transduce human DCs with a melanoma TAA gene (MART-1) and determine whether these transduced DCs could raise a specific antitumor response from quiescent autologous T lymphocytes. After retroviral transduction, human CD34+ cells were differentiated into DCs in vitro using granulocyte macrophage colony-stimulating factor, tumor necrosis factor alpha, and stem cell factor. This method consistently yielded a population of DCs as analyzed by morphology, phenotype, and MLR. Flow cytometric analysis revealed that 22-28% of cells expressing the DC phenotype also expressed a transduced marker gene. When DCs were transduced with the gene encoding MART-1, they stimulated much higher levels of cytokine release by MART-1-specific tumor-infiltrating lymphocytes than control DCs transduced with an irrelevant gene. In vitro stimulation using MART-1-transduced DCs but not control-transduced DCs raised specific antitumor CTLs from autologous quiescent T cells. These results provide evidence that human DCs can be retrovirally transduced with a TAA gene and that these transduced cells can raise a specific antitumor immune response in vitro. Transduced DCs may be useful for in vivo immunization against TAA.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Retroviridae
/
Células Dendríticas
/
Transfecção
/
Linfócitos do Interstício Tumoral
/
Vetores Genéticos
/
Melanoma
/
Epitopos
/
Antígenos de Neoplasias
Tipo de estudo:
Risk_factors_studies
Limite:
Humans
Idioma:
En
Revista:
Cancer Res
Ano de publicação:
1996
Tipo de documento:
Article
País de afiliação:
Estados Unidos