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- Title
Induction of ErbB-2/neu-specific protective and therapeutic antitumor immunity using genetically modified dendritic cells: enhanced efficacy by cotransduction of gene encoding IL-12.
- Authors
Chen, Y; Emtage, P; Zhu, Q; Foley, R; Muller, W; Hitt, M; Gauldie, J; Wan, Y
- Abstract
Overexpression of ErbB-2/neu occurs in 20-30% of patients with breast cancer and indicates a poor prognosis. The presence of a detectable immune response to ErbB-2/neu in some patients suggests that this oncogene may be a useful target for vaccine therapy. We evaluated whether genetic immunization using dendritic cells (DC) transduced ex vivo with an adenovirus expressing the ErbB-2/neu gene (AdNeu[sub TK]) could induce protective and therapeutic immunity against a breast tumor cell line overexpressing ErbB-2/neu. Subcutaneous (s.c.) immunization with the DC vaccine elicited protective immunity in an average of 60% of animals. CTL analysis demonstrated specific cytotoxic activity against breast tumor cells, as well as syngeneic fibroblasts transduced with AdNeu[sub TK]. In vivo depletion studies demonstrated both CD4[sup +] and CD8[sup +] T cells were required. In a therapeutic setting, immunization with the DC vaccines could cure mice with pre-established tumors and efficacy was further enhanced by cotransducing DCs with a vector expressing murine IL-12 (AdmlL-12). These studies support DC vaccines as a therapeutic strategy for human breast cancer, while emphasizing the importance of optimizing an immune response by combining tumor antigen presentation with immunostimulatory cytokines.
- Subjects
BREAST cancer gene therapy; GENE expression; DENDRITIC cells
- Publication
Gene Therapy, 2001, Vol 8, Issue 4, p316
- ISSN
0969-7128
- Publication type
Article
- DOI
10.1038/sj.gt.3301396