Engineered Attenuated Salmonella Typhimurium For Immunotherapies Of Cervical Cancer

Recently,cervical cancer has become a common type of cancer worldwide.Human papillomaviruses are the main carcinogen of cervical cancer.During the long-term infection of cervical tissues by human papillomaviruses,the virus-associated protein E7 plays a key role in the induction of cervical cancer and thus becomes a potential therapeutic target.The current treatments of advanced cervical cancer are still not optimistic.The combination of synthetic biology and tumor immunotherapies are expected to improve the treatments of cervical cancer.Tumor immune therapies based on oncolytic bacteria can ultimately inhibit the development and metastasis of tumors by stimulating and enhancing the immune system to recognize and kill tumors.In this paper,attenuated engineering Salmonella typhimurium was used to deliver therapeutic proteins into cervical cancer to stimulate anti-tumor immunity via genetic engineering and synthetic biology methods.This thesis demonstrated that attenuated engineered Salmonella typhimurium could express therapeutic proteins in cervical cancer mouse models by means of synthetic biology.The administration route of intratumoral injection can exert a certain anti-tumor immunity.In addition,nitroglycerin ointment could not stably promote the anticancer effects through the enhanced permeability and retention effects.In conclusion,this thesis applied attenuated engineering Salmonella typhimurium that express therapeutic protein drugs to treat cervical cancer in mouse models and explored the related anti-tumor immunity in various aspects,thus providing valuable evidences for the development of tumor immunotherapies against cervical cancer.