5.4.1　DNA Vaccine

DNA vaccines offer the opportunity to engineer protein and peptide antigen expression with more detailed design and delivery parameters, for example, to selectively express or assure suitable posttranslational modification of an antigen in the desired target cell and to enhance antigenicity and responsiveness.A vast number of preclinical studies involving numerous gene vaccines have established the capability to engender efficacious T cell-mediated tumor attacks against any number of target antigens [21].DNA vaccine is a technique for protecting an animal or human against diseases by injecting it with genetically engineered DNA, so cells directly produce an antigen [22].Back to the development of vaccines, the first generation of vaccine was the whole pathogen organism in live, weaken, or dead form.But there was a risk of induced disease by these vaccines.The second generation is a protein antigen derived from the pathogen.The third generation is DNA vaccine as well as RNA vaccine.The DNA expression vector is constructed by recombination and delivered to the body by injection or gene gun to produce the secretory or membrane binding antigen.Immunogenicity of DNA vaccine targeting tumor antigen generally is weak and not effective when it is used alone [23].The main trouble for DNA vaccines is the failure of inducing efficient immune responses in large animals, including human bodies, which is mainly due to the poor localization into the resident cells and lack of co-stimulatory molecules in local APCs [24].Therefore, novel approaches are needed to improve the efficiency of DNA vaccines.Except for subcutaneous or intradermal delivery, DNA vaccines can also be directly delivered into hosts’lymph nodes.This approach can improve the expression of co-stimulatory molecules and have been investigated in Phase I/II clinical trials in melanoma and other advanced solid tumor patients [25].To efficiently deliver DNA vaccines, many delivery technologies have been developed, including pressure injectors, ultrasound, liposome, nanoparticles, tattooing, gene gun and electroporation [26].The immunomodulator is another way to enhance the efficacy of DNA vaccine, which are built into the same plasmid encoding tumor antigens.The main types of immunomodulators including co-stimulatory molecules and signaling molecules, or stimulatory cytokines.Phase I studies in solid cancer patients has showed electroporated HER2/CEA DNA vaccine alone or combined with an adenoviral-based vaccine could induce measurable cell-mediated antigen-specific immune response[27].Another phase I/II trial reported a DNA fusion vaccine successfully induced CD8+ T-cell responses and increased PSA doubling time in prostate cancer patients [28].A novel adenoviral vector called Ad5 [E1-, E2b-]-CEA (6D) that can induce antigen specific cell-mediated immune responses in spite of the existence of Ad5-neutralizing antibody [29].(https://www.daowen.com)