Regional administration of oncolytic Echovirus 1 as a novel therapy for the peritoneal dissemination of gastric cancer.
The dissemination of malignant gastric cells to the peritoneum occurs frequently, usually as an early event in disease, and results in poor patient prognosis. Surgery and chemotherapy offer limited therapeutic success. The low-pathogenic human enterovirus, Echovirus 1 (EV1), is an oncolytic virus that selectively targets and destroys malignant prostate and ovarian cancer xenografts in vivo. Lytic EV1 infection requires the cell surface expression of alpha(2)beta(1), an integrin involved in the dissemination of gastric cancer cells to the peritoneum. Herein, we evaluated the capacity of EV1 for anti-neoplastic cell action in gastric peritoneal carcinomatosis. Flow cytometric analysis demonstrated that alpha(2)beta(1) was abundantly surface expressed on a panel of gastric cancer cell lines, rendering the majority of lines highly susceptible to in vitro lytic EV1 infection and supportive of efficient viral progeny production. A bioluminescent MKN-45-Luc SCID mouse model of peritoneal dissemination was developed to allow real-time non-invasive monitoring of peritoneal tumor burden. Employing this mouse model, we demonstrated a therapeutic dose-response for escalating oncolytic EV1 doses. Taken together, these results emphasize the exciting potential for EV1 as a single or adjunct therapy for the control of the peritoneal dissemination of gastric cancer.
Haley
Erin S
ES
The University of Newcastle, NSW, Australia.
Au
Gough G
GG
Carlton
Brian R
BR
Barry
Richard D
RD
Shafren
Darren R
DR
D000818:Animals; D045744:Cell Line, Tumor; D029822:Enterovirus B, Human / Q000502:physiology*; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D038982:Integrin alpha2beta1 / Q000032:analysis; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D008163:Luminescent Measurements / Q000379:methods; D051379:Mice; D008807:Mice, Inbred BALB C; D016513:Mice, SCID; D050130:Oncolytic Virotherapy / Q000379:methods; D050504:Oncolytic Viruses / Q000502:physiology; D010534:Peritoneal Neoplasms / Q000556:secondary / Q000628:therapy* / Q000821:virology; D010537:Peritoneum / Q000378:metabolism / Q000473:pathology / Q000821:virology; D013274:Stomach Neoplasms / Q000473:pathology / Q000628:therapy* / Q000821:virology; D016019:Survival Analysis; D014162:Transfection; D047368:Tumor Burden; D023041:Xenograft Model Antitumor Assays
D038982:Integrin alpha2beta1; D008156:Luciferases