Induction of protective and therapeutic antitumour immunity using a novel tumour-associated antigen-specific DNA vaccine.

DNA vaccination has become an attractive immunization strategy against cancer. However, a major problem of DNA vaccination is its limited potency to be taken up by the antigen-presenting cells. In contrast, loss of immunogenic epitopes of tumour cells has urged the development of vaccines against multiple epitopes. In this study, we developed a novel strategy for the APC to efficiently cross-present a fusion tumour antigen, which contains both MHC class I-restricted and class II-restricted T-cell epitopes from Her-2/neu and p53 in a cognate manner. The N-terminus of the fusion Her-2/neu, p53 protein was linked to the sequence encoding for human secondary lymphoid-tissue chemokine for secretion and chemokinesis, and the C-terminus of the fusion protein was linked to a cell-binding domain of IgG (Fc portion, the cell-binding domain of IgG) for receptor-mediated internalization. Here, we show that the introduction of fused-gene DNA vaccine by gene gun reduced the size of established tumours and prolonged the lifespan of tumour-bearing mice. Results show that this DNA vaccination strategy can broadly enhance the antigen-specific cellular and humoral immune responses. This vaccine is capable of inducing adaptive immunity and may provide a novel, generic design for the development of therapeutic and preventive DNA vaccines.