Vaccination with liposome--DNA complexes elicits enhanced antitumor immunity

Cationic liposomes have been shown to potentiate markedly the ability of plasmid DNA to activate innate immune responses. We reasoned therefore that liposome-DNA complexes (LDC) could be used to produce more effective plasmid DNA vaccines for cancer. To test this hypothesis, tumor-bearing mice were vaccinated with conventional plasmid DNA vaccines or with LDC vaccines encoding model tumor antigens and CD8(+) T-cell responses and antitumor activity were assessed. We found that although plasmid DNA vaccines generated large increases in antigen-specific CD8(+) T cells, they failed to elicit significant antitumor immunity. In contrast, LDC vaccines elicited large numbers of antigen-specific CD8(+) T cells and also generated significant antitumor activity against established tumors. The antitumor activity elicited by immunization with LDC vaccines was mediated primarily by CD8(+) T cells. Studies of the interaction of LDC with antigen-presenting cells found that LDC triggered dendritic cell production of interleukin-12 and interferon (IFN)-gamma production by natural killer cells in vivo. Activation by LDC was also accompanied by upregulation of costimulatory molecule expression. These findings suggest that by concurrently activating strong systemic innate immune responses and generating cytotoxic T-lymphocyte responses, LDC may be used to increase the effectiveness of therapeutic plasmid DNA vaccination for cancer.