PD1 Antibody Inhibits Prostate Cancer Growth And Development In Vivo

Background:Prostate cancer(PCa)is the most common cancers and the second leading cause of death in men in western countries.In recent years,with the improvement of clinical testing and treatment methods,the mortality rate of prostate cancer in 2014 decreased by 51%compared with that in 1993.However,traditional treatments of prostate cancer,such as surgery,radiotherapy and chemotherapy could not deliver effective treatment for patients.Malignant tumors,particularly the advanced tumors and metastatic cancers,induced immune tolerance in vivo and metastasis causing the immune response ineffective in killing tumor cells.Thus,the tumor is not sensitive or even resistant to single treatment.Therefore,combination therapy could be a new therapeutic approach replacing traditional radiotherapy and chemotherapy.At present,the activation of the monoclonal antibody drugs targeting programmed death 1(PD1)/programmed death ligand 1(PD-L1)is a hot spot in tumor biotherapy.The promising results have been proved in non-small cell lung cancer and melanoma,and in clinic,also improved clinical progress and prognosis of patients with tumor.PD1 and PD-L1,act as the important negative immune regulatory factors,are closely related to tumor growth,metastasis,drug resistance and poor prognosic.The Binding of PD1 receptor expressed on T cell and PD-L1 ligand expressed on the surface of tumor cells regulate the transmitment of control signals,and inhibite T cell activation and proliferation,finally contribute to the immune escape of tumor cells and the conventional chemotherapy resistance.In this study,the effect of PD1 antibody itself and the combination of paclitaxcel and PD1 antibody were compared with the prostate cancer animal model.And the growth of tumors was inhibited more obviously by the combination of paclitaxcel and PD1 antibody,compared with the PD1 antibody itself.The results showed that the PD1 antibody maight be a potential target for prostate cancer therapy and the combination of it with some antitumor drugs may provide new theoretic support for clinical treatment.Part one:PD1 antibody inhibits the growth of prostate cancer xenografts in vivoObjective:To investigate whether PD1 antibody could inhibit the gowth of prostate cancer xenografts.Methods:We established the subcutaneous prostate cancer animal model by injecting 1×10~6(cells/mice)of RM1 cells subcutaneously into C57BL/6 male mice.When the subcutaneous tumor was approximately extended to 50mm~3,we need to:1)distribute C57BL/6 male mice into four new groups;2)inject with PD1 antibody,paclitaxel and its combining with PD1 antibody once a week by intraperitonealion among different treatment groups;3)measure the subcutaneous tumor size and body weight of C57BL/6 male mice twice a week;4)C57BL/6 male mice was proceeded bioluminescence imaging in vivo once a week.When the tumor size was about 1000mm~3,the mice were sacrificed and the tumor was removed.Results:The growth rate of the subcutaneous tumor in the paclitaxel positive control group,the PD1 antibody group and its combinaition group was lower than that in the PBS control group,of which the combination of PD1 antibody with paclitaxel group showed the lowest growth rate.Conclusion:PD1 antibody,as a single monoclonal antibody drug,might inhibit the growth of prostate cancer subcutaneously.And the growth of tumors was inhibited more obviously by the combination of paclitaxcel and PD1 antibody,compared with the PD1 antibody itself,indicating that PD1 antibody might act as a new target for antitumor immunotherapy.Part two: The role of PD1 antibody in prostate cancer metastasisObjective: To investigate whether PD1 antibody exhibit an obviously effect on blocking prostate cancer metastasis.Methods: We established the intracardiac injection prostate cancer animal model by intracardiac injecting 1×105(cells/mice)of RM1 cells into C57BL/6male mice.After two days later,we need to: 1)inject with PD1 antibody,paclitaxel and its combining with PD1 antibody once a week by intraperitonealion among different treatment groups;2)measure the body weight of C57BL/6 male mice twice a week;3)proceed bioluminescence imaging in vivo in 6th day for the first time;4)inject with PD1 antibody,paclitaxel and its combining with PD1 antibody for the second time by intraperitonealion among different treatment groups;5)kill the C57BL/6 male mice and proceed bioluminescence imaging with organ in vitro.Results: After establishing the intracardiac injection prostate cancer animal model for one week,prostate cancer metastasis appeared in lung.The metastasis intensity of positive control group(paclitaxel),PD1 antibody group itseft and PD1 monoclonal antibody combined with paclitaxel group compared with control group showed little difference.However,the overall survival rate of C57BL/6 mice in PD1 antibody treatment groups were higher than that of the PBS control group.Conclusion: The PD1 antibody,as a single monoclonal antibody drug,has a tendency to decrease prostate cancer metastasis.Particularly,PD1 antibody might improve the overall survival rate of cardiac injected mice.Therefore,PD1 antibody may be a new antitumor immunotherapy targeted for prostate cancer mestastsis.