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Oncolytic Virotherapy Development for Gastrointestinal Cancers

Gastrointestinal cancer refers to malignant conditions of the gastrointestinal tract (GI tract) and accessory organs of digestion, including the esophagus, stomach, biliary system, pancreas, small intestine, large intestine, rectum and anus. As a novel strategy, immunotherapy is emerging as an effective and promising treatment against several types of cancer, and it has shown encouraging results in various pre-clinical and clinical studies. In spite of the current clinical benefit seen from the treatment of GC, colorectal cancer, and pancreatic cancer using immune check point inhibitor antibody against CTLA-4, PD-1, or PD-L1, which are three major immune checkpoint molecule targets, oncolytic virotherapy is arising as an another promising treatment strategy and several studies have shown that oncolytic virus shows considerable antitumor efficacy in gastrointestinal cancers. On the basis of Creative Biolabs’s oncolytic virus development platform OncoVirapy™, coupled with our enhancing understanding of tumor oncology in GI cancers, our scientists are capable of developing specific oncolytic virotherapy strategy followed by providing oncolytic virus construction and validation services.

Oncolytic Virotherapy Development for Gastrointestinal Cancers Fig.1 The pathogenesis of gastric cancer involves both environmental factors and genetic susceptibility (McLean, M. H., 2014)

Gastric Cancer

Gastric Cancer (GC) is the fifth most common malignancy in the world, with almost 1 million new cases annually. Upper GI tracts are a group of highly aggressive malignancies. Despite that environmental factors play critical role in the pathogenesis of GC, identification of genetic alteration still contributes enormously to the understanding of GC and will lead to better design of therapy strategy. Based on recent studies, it remains to be a better choice that combining oncolytic virus with other therapy strategies, such as those treatments that adopt antibodies to alter the tumor microenvironment by inhibiting tumor angiogenesis or treatment that use immune checkpoint inhibitors to improve the T cell function. Besides, oncolytic virus can also be used as monotherapy through arming with other antitumor elements.

Pancreatic Cancer

Pancreatic Cancer occurs when cells in the pancreas begin to multiply out of control, and these malignant cells invade other parts of the body. Among various types of pancreatic cancer, pancreatic adenocarcinoma accounts for about 85% of cases, and after 45 years of study, it remains a highly lethal disease that is extremely difficult to detect and treat. Unfortunately, targeted agents and chemotherapies for pancreatic cancer have only minor improved clinical outcome. For now, oncolytic virus is becoming increasingly popular for treatment of many types of cancers, due to its tumor selectivity and cancer killing ability. Moreover, oncogenic alteration in pancreas is currently understood to be a multistage process, which can be exploited to design the oncolytic virus of greater specificity and potency. To specify, the most common mutation is in the KRAS gene, followed by mutation in the tumor suppressor genes TP53.

With the need of novel therapeutic strategies in gastrointestinal cancers, oncolytic virus continues to hold promise as an effective treatment. Creative Biolabs will keep striving to exploit this novel approach to cross the remained barriers and to develop more efficient oncolytic virotherapy strategies for our customers.

Reference:
  1. Zin W. Myint, Gaurav Goel, (2017). “Role of modern immunotherapy in gastrointestinal malignancies: a review of current clinical progress” Journal of Hematology & Oncology (2017) 10:86
  2. Robin J. Prestwich, Kevin J. Harrington, (2008). “Oncolytic viruses: a novel form of immunotherapy.” Expert Review of Anticancer Therapy (2008) 8
  3. McLean, M. H., El-Omar, E. M. (2014) “Genetics of gastric cancer.” Nat. Rev. Gastroenterol. Hepatol (2014) 143

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