Targeting Therapy For Prostate Cancer By DD3-Driven Oncolytic Adenovirus-Harboring IL-24

The process of cancer,is a multistep pathogenesis caused by the accumulation of errors in key regulatory pathways.The cancer originated one cell,then proliferation and gain the extra changes than surrounding normal cells to the survival.These altered cells produce thousands of cancer cells through proliferation.The causes of cancer are various.Age,living habits and family inheritance may lead to the development of cancer.The occurrence of prostate cancer,generally speaking,is due to the uncontrolled growth of the acinar cells in the prostate.These cells have grown in the unnormal state,and their cell morphology and function have changed.Because of the objective environmental factors,the incidence of prostate cancer in western countries is far beyond our country.However,in recent years,the incidence of prostate cancer in China has increased year by year.Currently,there are two ways to treat prostate cancer,including surgery and radiotherapy,but the prognosis is poor.As early as 2009,gene therapy was selected as the ten largest global achievement of the science magazine,but because of its use of non replicative vector,the effection of cancer treatment was not significant.Our laboratory uses a replicative oncolytic virus vector,inserts the gene into a replicative vector,and creatively combines gene therapy with the treatment of the oncolytic virus,so that when the virus is replicated,the genes that are inserted into the viral vector are also replicated,which greatly expands the therapeutic effect.This treatment is called Cancer Targeting Gene-ViroTherapy(CTGVT).We constructed an oncolytic adenovirus OncoAd-DD3-E1A-ΔE1B-IL24,briefly,OncoAd-IL24.OncoAd-IL24 decreased PCa cell viability to a greater degree than either OncoAd,while there were no toxicity to human normal prostate cells,human primary liver fibroblasts and prostatic fibroblasts.OncoAd-IL24 also induced apoptosis and autophagy in 22RV1 cell and LNCaP cell.Intratumoral injection of OncoAd-IL24 repressed tumor growth and effectively inhibited tumor metastasis in LNCaP xenograft model.In addition,the immunohistochemical results showed that OncoAd-IL24 could significantly inhibit angiogenesis in the transplanted tumor.The above results suggest that oncolytic adenovirus combined with anti-cancer genes provides a new strategy for prostate cancer treatment.