胰腺癌是一种高度恶性消化系统肿瘤，当前缺乏有效治疗方法。溶瘤腺病毒在肿瘤治疗中得到广泛研究，但其在胰腺癌治疗的临床研究尚未取得较大进展。已有文献报道溶瘤病毒联合光动力治疗肿瘤，但由于肿瘤组织普遍乏氧，严重制约光动力疗效。我们查阅文献及预实验发现，胰腺癌细胞癌变过程中产生大量过氧化氢，而过氧化氢酶（CAT）可将其转化为水和氧，进而改善肿瘤组织乏氧。因此，本项目拟构建表达CAT和光动力蛋白KillerRed的溶瘤腺病毒，使其能在裂解肿瘤同时表达CAT降解胰腺癌中过量的过氧化氢而产氧，为光动力杀伤肿瘤提供氧源，增强抗肿瘤疗效。此外，我们还拟在病毒E1A基因下游插入胰腺癌中显著低表达的miRNA互补序列，提高其对胰腺癌的靶向性和安全性。本研究拟在细胞和动物水平对构建的具有胰腺癌靶向性的自供氧联合光动力新型溶瘤腺病毒治疗胰腺癌能力进行深入研究，预期研究成果可为胰腺癌生物治疗提供新方法。

Pancreatic cancer is a highly malignant tumor of the digestive system, currently there is no effective treatment. Oncolytic adenovirus has been widely studied in tumor therapy, but its application in pancreatic cancer has not made great progress. Oncolytic virus combined with photodynamic therapy has been reported in the literature, but the efficacy of photodynamic therapy is seriously restricted due to the general hypoxia of tumor tissues. We reviewed literatures and preliminary experiments, then found that a large amount of hydrogen peroxide (H2O2) is produced during the carcinogenesis of pancreatic cancer cells, which can be converted into water and oxygen by catalase (CAT). Therefore, this project intends to construct oncolytic adenovirus expressing CAT and photodynamic protein KillerRed, so that it can simultaneously express CAT to degrade excessive H2O2 in tumor and produce oxygen, providing an oxygen source for photodynamic tumor killing and enhancing anti-tumor efficacy. In addition, we intend to insert the complementary sequences of miRNA which significantly low-expressed in pancreatic cancer downstream of virus E1A gene to improve oncolytic targeting and safety for pancreatic cancer. In conclusion, we intend to conduct an in-depth study on the ability of self-oxygenation combined with photodynamic novel oncolytic adenovirus in the treatment of pancreatic cancer at the cellular and animal levels, and expect that the research results can provide new methods for the biological treatment of pancreatic cancer.