Study Of Therapeutic Tumor Gene Vaccine Targeting Survivin And MUC1VNTR

Cancer is such a fatal disease， which million.s. of people die from. With morepressure and unhealthy daily routines, increasingly younger people are sufferingfrom cancer. The main therapy of cancer in clinical are surgery, radiotherapy andchemotherapy, and the three anti-cancer therapies have helped many patients relievethe pain, but they are not effective enough to eradicate the tumor. Recent decadesimmunotherapy has played an important role in the cancer research and clinical use.Chemotherapy depends on the anticancer agents which is cytotoxic and inducesthe tumor cell death, however, which is also limited by its toxic effects towardnormal tissues. Immunotherapy aims at activating the immune system by tumorassociated antigen or tumor specific antigen to eradicate the tumor, which has betterspecificity to tumor tissue comparing with chemotherapy. There are accumulatingevidence to suggest that the chemotherapy drug can also help to activate the immunespecific cellular respon.s.es. Moreover, the cancer vaccine can sen.s.itize the tumorcells to the chemotherapeutic drug. All these results indicates that the combination ofchemotherapy and immunotherapy is a potential method.We use tumor gene vaccine combined with chemotherapeutics to control thetumor growth and prolong the life time of mice bearing tumor. The gene vaccinecon.s.ists of the plasmid DNA and recombinant adenovirus. The plasmid DNAvaccine has two candidates, CpDV-IL2-MS and CpVR-MS with VR-IL2separately(CpVR-MS/VR-IL2) all of which have gained earlier. The two candidates have thesame factors, survivin and MUC1(MS), two tumor associated antigens, CpG motif(Cp) and interleukin-2(IL-2) are used as adjuvants, which can help the survivin andMUC1to activate the immune system. The gene of survivin and MUC1(MS) werealso in.s.ert into the adenovirus and we gained the recombinant adenovirus (rAD).In the research, we aim at solving three questions. First，since CpDV-IL2-MShas the same immunogen and adjuvants with CpVR-MS/VR-IL2, wehther the former could have the same anticancer capacity. The results show no significantdifferences in terms of suppression of tumor growth and prolonging the life time.Second, whether the anticancer effect will be enhanced when the two gene vaccinesare vaccinated in company with chemotherapy drugs. The results indicate that theeffects are improved when the mice are treated gene vaccine together withoxaliplatin, and the ability of CpDV-IL2-MS of prolonging the life time is stillstrong when the dose of oxaliplatin was reduced to the half. Third, the gene vaccineis composed of plasmid and adenovirus, what kind of immune strategy is better，theDNA prime adnovirus boost or the adnovirus prime DNA boost? We found that thetwo immune strategy show no significant differences, and the former is moreeffective in the term of prolonging the life time of tumor-bearing mice.In conclusion, all of the results indicate that CpDV-IL2-MS could well play thesame antitumor effect as CpVR-MS/VR-IL2, and the effect could be improved whenit is combined with oxaliplatin；and we have got a better immune strategy thatplasmid CpDV-IL2-MS is vaccinated twice to prime the immune system, and rAD isused to boost.