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Viro-immune therapy:A new strategy for treatment ofpancreatic cancer

World Journal of Gastroenterology 2016年第2期22卷 748-763页

作者： Andrea Marie Ibrahim Yao-he Wang Centre for Molecular Oncology Barts Cancer InstituteQueen Mary University of LondonEC1M6BQ LondonUnited Kingdom National Centre for International Research in Cell and Gene Therapy Sino-British Research Centre for Molecular OncologyZhengzhou UniversityZhengzhou 450000Henan provinceChina

Pancreatic ductal adenocarcinoma(PDAC) is an almost uniformly lethal disease with less than 5% survival at five years. This is largely due to metastatic disease, which is already present in the majority of patients when diagnosed. Even when the primary cancer can be removed by radical surgery, local recurrence occurs within one year in 50%-80% of cases. Therefore, it is imperative to develop new approaches for the treatment of advanced cancer and the prevention of recurrence after surgery. Tumour-targeted oncolytic viruses(TOVs) have become an attractive therapeutic agent as TOVs can kill cancer cells through multiple mechanisms of action, especially via virus-induced engagement of the immune response specifically against tumour cells. To attack tumour cells effectively, tumour-specific T cells need to overcome negative regulatory signals that suppress their activation or that induce tolerance programmes such as anergy or exhaustion in the tumour microenvironment. In this regard, the recent breakthrough in immunotherapy achieved with immune checkpoint blockade agents, such as anti-cytotoxic T-lymphocyte-associate protein 4, programmed death 1(PD-1) or PD-L1 antibodies, has demonstrated the possibility of relieving immune suppression in PDAC. Therefore, the combination of oncolytic virotherapy and immune checkpoint blockade agents may synergistically function to enhance the antitumour response, lending the opportunity to be the future for treatment of pancreatic cancer.

关键词： anti-cytotoxic T-lymphocyte-associateprotein 4 Anti-programmed death receptor ligand 1 Anti-programmed death receptor 1 Immunotherapy Oncolytic viruses Pancreatic ductal adenocarcinoma Pancreatic cancer Immune checkpoint blockadeinhibitors cancer vaccine

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