Combined Therapeutic Benefit Of Anti-PD1/CD137in Murine Ovarian Cancer

Ovarian carcinoma is the most common malignent cancer in women,90%of which isEpithelial ovarian carcinoma.The traditional theraputic therapy is surgicaldebulk,chemotherapy or radiotherapy.however,more than70%women of EOC willexperience disease recurrence and metastasize in the peritoneal cavity.the traditional treatmentfor ovarian cancer is surgical debulking,then platinum based chemotherapy following aim toclear the microfoci which can not cut by surgical.However,badly,the most patients willrecurrence and die.The treatment also make patients pain and have poor live quality.Toconquer the high ratio of recurrence,release pain,to improve live quality of the patients,weneed to made a new stratigy to have a better therapeutic efficacy.As the develop of the immunology technology,more and more tumor-associated antigenwas be found and researched. Scientists now design some immunology theraputies to thetumor antigen aim to clear the microfoci that metastasized.there are kinds of efficacy onmelanoma and renal cell carcinoma.Immunoregulate antibody can regulate organic immune system,such as it can connectwith co stimulatory receptor of T cell to boosting T cell activity,or connect with co inhibitoryreceptor to inhibite T cell program death.There are a lot of receptors about T cell’s functionsignals researched,for example, CD28,CD137,CTLA4,PD1,TIM3,LAG-3.The monoantibodies aganst these receptors were used to treat melanoma and renal cellcarcinoma,and have a promised outcome.However,this immunotherapy was not yet used inovarian cancer,so we next will use this methord to stimulate T cell function aim to receive abetter efficacy.In this experience,we established a ID8murine ovarian cancer model,and then use aimmunotherapeutic strategy to treatment.Firstly,we compared anti-CD137/PD1monoantibodies and other monoantibodies involved other immune-modulatory such asCD40,TIM,LAG-3.Which are two combine used or single.we find Combinatorial PD-1andCD137has better therapeutic efficacy in ID8mouse cancer models and Synergizes withCisplatin,the mean survival time reached90days in the treatment group.Then we researched the mechanism involved.We analysed the subtypes’ changes in spleens and peritoneal cavityof treated mice by flow cytometry.We also analysed the anti-tumor specific CTLs by elispotkit.The experience gives us a result that is combinate anti-cd137/PD1improved the ratio andabsolute number of CD8+T cell,reduced the ratio of immunosuppress Treg and MDSC aswell as their absolute number.The ratio of CD8+T cell to immunosuppress cell wassignificantly improved.More importantly,the CD8+T cell was activated,and product highlevel of IFN-gamma,have antigen special CTLs,which was stimulated by muticolone or TAA.