Viro-immune therapy: A new strategy for treatment of pancreatic cancer

Abstract

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.

Keywords: Anti-cytotoxic T-lymphocyte-associate protein 4, Anti-programmed death receptor ligand 1, Anti-programmed death receptor 1, Immunotherapy, Oncolytic viruses, Pancreatic ductal adenocarcinoma, Pancreatic cancer, Immune checkpoint blockade inhibitors, Cancer vaccine

Core tip: The poor prognosis of pancreatic cancer appeals for a novel strategy to treat this disease. Immunotherapies such as whole cell vaccines are currently being investigated in patients with pancreatic cancer. The recent breakthrough in cancer immunotherapy with immune checkpoint inhibitors has allowed us to reverse T cell anergy and enhance antitumour immunity. Tumour-targeted Oncolytic viruses in combination with checkpoint inhibitors function synergistically to increase the tumour antigen load, relieve immune suppression in the tumour bed while enhancing the activation of the adaptive immune system. Viro-immune-checkpoint therapy should thus be considered as a novel strategy to treat pancreatic cancer.