Vaccination with liposome–DNA complexes elicits enhanced antitumor immunity

Abstract

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 þ T-cell responses and antitumor activity were assessed. We found that although plasmid DNA vaccines generated large increases in antigen-specific CD8 þ T cells, they failed to elicit significant antitumor immunity. In contrast, LDC vaccines elicited large numbers of antigen-specific CD8 þ 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 þ 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)-g 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.

Protection from Pneumonic Infection withBurkholderiaSpecies by Inhalational Immunotherapy

“…Previous studies have indicated that NK cells were the major source of IFN-␥ production following systemic (i.v.) treatment with CLDC (10,34). However, the role of NK cells in mediating CLDC-induced pulmonary immunity to bacterial challenge has not been explored previously.…”

Synthesis and delivery activity of new cationic cholesteryl glucosides

“…Among synthesized cholesterol derivatives, there is a commercially available lipid, 3-b-[N-(N 0 ,N 0 -dimethylaminoethyl)carbamoyl]-cholesterol (DC-Chol). Liposomes prepared with DC-Chol and DOPE lipids are widely used to deliver the plasmid DNA for tumor immunotherapy 19,20 or artificial immunization 21 and are under clinical trials for the therapy of mucoviscidosis. 22 As mentioned above, lipids with different positively charged groups based on aliphatic or heterocyclic bases were synthesized to reveal the structure-activity relationships between the structure of cationic lipids and the transfection activities.…”

DNA vaccines, electroporation and their applications in cancer treatment

“…For instance, liposome-DNA vaccine complex was more effective at increasing CD8+ T cell numbers and controlling established tumors through the production of IL-12 from dendritic cells and of IFN- from NK cells, as compared with DNA vaccines alone. 71 Similarly, higher anti-melanoma immune responses were elicited by formulation of DNA vaccines with nanoparticle, as compared with DNA vaccines alone. 72 Thus, the use of these formulations and newer delivery strategies likely hold promise for augmenting the potency of cancer DNA vaccines.…”