| Background Gastric cancer is among the most common malignant tumors in China and is mainly treated by surgery and chemotherapy. However, those conventional therapies cannot deal with such problems as tumor metastasis and recurrence. Cancer immunotherapy is a rather new field of tumor therapy, which includes monoclonal antibodies, tumor vaccines, immune response modifiers, such as Interferon-a, Interleukin-2 and Interleukin-12. But now there is no effective gastric cancer vaccine developed yet. MG7-Ag is a specific marker molecule of gastric cancer, which was discovered by our institute. Its antigenicity was found to locate in a sugar chain, which means it is a carbohydrate antigen. Carbohydrate antigens are intrinsically T- cell-independent antigen, often eliciting a short-lived IgM response of poor memory without inducing a T-cell response. It is also hard to purify or mass-produce carbohydrate antigen. One way tosolve these problems is to substitute carbohydrate antigen with peptides that could mimic the original antigen, which has been proved in many animal experiments. By screening the phage display library, a series of mimicry peptides were identified in our institute. Competitive antibody binding assay indicated that the mimicry peptides could mimic MG7-Ag well, and analysis with computer showed that the mimicry peptides could bind with HLA molecules.DNA vaccine is now widely used in lab research because of its ability to induce specific, effective and persisting immunity. It also can mimic the processing and presenting of endogenous antigen, thus inducing T cell response. The immunizing pathways of DNA vaccine include intramuscular injection, intradermal injection, skin gene gun bombard and intraveinous injection. Many DNA vaccines have been evaluated in clinical trials, such as DNA vaccines against melanoma, B cell lymphoma, HIV, HBV and plasmodium, in which most of them were given by intramuscular injection. It is implicated that the DNA vaccine are well tolerated by human body.To enhance the effect of epitope-based gene immunization, several strategies could be adopted: fusion or coinjection of cytokines; fusion of the epitope to a carrier protein; combination of multiple epitopes, etc.Multi-epitope vaccine induces specific immune response against each epitope in the vaccine. And the potency of repeated-epitopevaccine could be improved because the epitope's copy is increased and Thl response is enhanced. When several epitopes are combined together, flanking sequence will affect the potency of the vaccine. Therefore, it is crucial to insert spacers between epitopes. Proper spacer can prevent mutual interference between epitopes and unspecific binding with MHC molecules.Oligopeptides are degraded easily in vivo and require carrier proteins to protect them. Heat shock protein 70 is a molecular chaperon in the pathway of MHC I-dependent antigen processing. It can stabilize the peptide and transfer it to endoplasm reticulum. Acting as a immune stimulator, HSP70 can up regulate the expression level of cytokines. Therefore, HSP70 is a good carrier of vaccine. Vaccines based on HSP70 have been explored in clinical research. The HSP70-peptide complex derived from tumor tissues or recombined in vitro can induce specific anti-tumor response. Similar effect could be obtained with the fusion gene of HSP70 and peptides.Another approach to improve the immunogenicity of DNA vaccine is through the co-delivery of chemokine expression plasmid or fusion of the antigen to chemokines. Studies in a variety of infectioius disease clearly demonstrate that chemokine could alter the magnititude and direction of the immune response elicited by DNA vaccine. MIG and IP-10 not only recruit immune cells such as T cells, NK cells, but also inhibit angiogenesis, which makes them especially fit for tumorvaccine. However, many human involve a complex chemokine network that may influence the extent and phenotype of the leukocyte infiltration, angiogenesis, tumor cell growth , survival and metastasis. Chemokine rereptors exp...
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