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Review
. 2016 Jan 14;22(2):748-63.
doi: 10.3748/wjg.v22.i2.748.

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

Andrea Marie Ibrahim  1 , Yao-He Wang  1
Affiliations
Review

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

Andrea Marie Ibrahim et al. World J Gastroenterol. .

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 1; Anti-programmed death receptor ligand 1; Cancer vaccine; Immune checkpoint blockade inhibitors; Immunotherapy; Oncolytic viruses; Pancreatic cancer; Pancreatic ductal adenocarcinoma.

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Figures

Figure 1
Figure 1
Synergistic effects of viro-immunotherapy. Systemic administration of a tumour-targeted oncolytic virus (TOV) leads to vasculature destruction allowing the invasion and infection of the tumour cells. As the TOV selectively replicates within a tumour cell, it infects neighboring cells leading to the amplification of the virotherapy and induction of the innate immune system. Direct oncolysis allows the release of tumour-associated antigens into the microenvironment, which are presented by antigen-presenting dendritic cells (DCs) to naïve T cells in the draining lymph nodes, activating the adaptive tumour-specific response. The administration of an immune checkpoint blockade antibody such as an anti-PD-L1 antibody provides an added benefit of reversing T cell anergy. This allows the antitumour response induced by the virotherapy to be enhanced and sustained. The combination of viro-immunotherapy may have significant synergistic effects in such an immunosuppressive microenvironment as seen in pancreatic ductal adenocarcinoma. CAF: Cancer-associated fibroblast; ; PSC: Pancreatic stellate cell; TAM: Tumour-associated macrophage.
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