Oncolytic virotherapy in hepato-bilio-pancreatic cancer: The key to breaking the log jam?

Abstract

Traditional therapies have limited efficacy in hepatocellular carcinoma, pancreatic cancer, and biliary tract cancer, especially for advanced and refractory cancers. Through a deeper understanding of antitumor immunity and the tumor microenvironment, novel immunotherapies are becoming available for cancer treatment. Oncolytic virus (OV) therapy is an emerging type of immunotherapy that has demonstrated effective antitumor efficacy in many preclinical studies and clinical studies. Thus, it may represent a potential feasible treatment for hard to treat gastrointestinal (GI) tumors. Here, we summarize the research progress of OV therapy for the treatment of hepato-bilio-pancreatic cancers. In general, most OV therapies exhibits potent, specific oncolysis both in cell lines in vitro and the animal models in vivo. Currently, several clinical trials have suggested that OV therapy may also be effective in patients with refractory hepato-bilio-pancreatic cancer. Multiple strategies such as introducing immunostimulatory genes, modifying virus capsid and combining various other therapeutic modalities have been shown enhanced specific oncolysis and synergistic anti-cancer immune stimulation. Combining OV with other antitumor therapies may become a more effective strategy than using virus alone. Nevertheless, more studies are needed to better understand the mechanisms underlying the therapeutic effects of OV, and to design appropriate dosing and combination strategies.

Keywords: biliary tract cancer; hepatocellular carcinoma; immunotherapy; oncolytic virus; pancreatic cancer.

Figure 1

(1) OVs induce immunogenic cell death (ICD). Then oncolysis by OVs causes the release of tumor‐specific antigens (local oncolysis); (2) ~ (3) Tumor‐specific antigens uptake by APCs which migrate to lymph nodes. Antigen‐loaded APCs initiate the activation of tumor‐specific T cells; (4) ~ (5) Tumor‐specific T cells move to local tumor mass (infected) and metastatic cancer cells (uninfected) and exert antitumor effect

Figure 2

Number of published or registered preclinical and clinical studies for oncolytic virus in hepato‐bilio‐pancreatic cancer Adenovirus is the most widely used. There are few related clinical trials, and most of the existing clinical trials are only in Phase I or Phase II clinical trials

Figure 3

Properties of the oncolytic viruses for hepato‐bilio‐pancreatic cancer and several well‐validated oncolytic viruses are listed. The yellow region represents the capsid and the blue region represents the envelope. Both adenovirus and reovirus are non‐enveloped viruses. The values represent the range of minimum diameter of the capsid. dsDNA, double‐stranded DNA; ssRNA, single‐stranded RNA