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. K E Y W O R D Sbiliary tract cancer, hepatocellular carcinoma, immunotherapy, oncolytic virus, pancreatic cancer 2944 |

Immunotherapy as a Therapeutic Strategy for Gastrointestinal Cancer—Current Treatment Options and Future Perspectives

“…Based on research on the combinational treatment of bevacizumab and atezolizumab in inoperable HCC, survival was significantly improved 84.8% for six months and 67.2% for 12 months, while for sorafenib it was 72.2% and 54.6%, respectively. At the same time, the progression-free interval was better (around 6.8 months) for the combinational therapy of atezolizumab–bevacizumab compared to monotherapy with Sorafenib (around 4.3 months) [ 112 ]. Lastly, the phase III study (RATIONALE-301) evaluated tislelizumab in comparison with sorafenib, as first-line systemic therapy, with promising anti-cancer effect for HCC, while another phase 3 (LEAP-002) study assessed the combinational treatment of Pembrolizumab (IV infusion on day 1 of every 21-days cycle, for 24 months) and lenvatinib (oral administration of 12 or 8 mg for body weight ≥60 kg or <60 kg, respectively) as first-line systemic therapy for patients with advanced HCC [ 113 ].…”

Engineering Gene Therapy: Advances and Barriers

“…[ 222,223 ] Pexa‐Vec is currently being evaluated in a phase III clinical trial for patients with advanced hepatocellular carcinoma (HCC). [ 224 ] Several engineered VACV vectors termed MVA, NYVAC, ALVAC, MVA‐5T4, rV‐PSA, TG4010, and PANVAC have been reported in clinical trials for cancer therapy and vaccine development. As they are highly attenuated, host‐restricted, poorly, or non‐replicative.…”

Immunotherapies for hepatocellular carcinoma

“…There are currently several clinical trials underway exploring the efficacy of OVs and ICIs in combination for the treatment of multiple solid tumour sites 134,135 . In the context of HCC, OVs hold potential to sensitise the immune‐tolerant microenvironment and to immunologically prime tumours for ICI activity 131,136 …”

“… 134 , 135 In the context of HCC, OVs hold potential to sensitise the immune‐tolerant microenvironment and to immunologically prime tumours for ICI activity. 131 , 136 …”