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

Overexpression of ErbB-2/neu occurs in 20-30% of patients with breast cance r and indicates a poor prognosis. The presence of a detectable immune respo nse to ErbB-2/neu in some patients suggests that this oncogene may be a use ful target for vaccine therapy. We evaluated whether genetic immunization u sing dendritic cells (DC) transduced ex vivo with an adenovirus expressing the ErbB-2/neu gene (AdNeu(TK)) could induce protective and therapeutic imm unity against a breast tumor cell line overexpressing ErbB-2/neu. Subcutane ous (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 tran sduced with AdNeu(TK). In vivo depletion studies demonstrated both CD4(+) a nd CD8(+) T cells were required. In a therapeutic setting, immunization wit h the DC vaccines could cure mice with pre-established tumors and efficacy was further enhanced by cotransducing DCs with a vector expressing murine I L-12 (AdmIL-12). These studies support DC vaccines as a therapeutic strateg y for human breast cancer, while emphasizing the importance of optimizing a n immune response by combining tumor antigen presentation with immunostimul atory cytokines.