Chimeric oncolytic Ad5/3 virus replicates and lyses ovarian cancer cells through desmoglein-2 cell entry receptor.

ABSTRACT: Despite new therapies, the estimated 229?875 women living with ovarian cancer have a 5-year survival rate of 47.6%. This cavity-localized cancer lends itself to local administration of modalities, such as the oncolytic adenovirus (Ad) Ad5/3-D24-granulocyte-macrophage colony-stimulating factor virus (ONCOS-102). Its repeated administration to a patient with chemotherapy-refractory ovarian cancer induced CD8+ antitumor immune responses with the overall survival reaching 40 months. Here we probe the dominant receptor used by ONCOS-102 in four established epithelial ovarian cancer cell lines. Ad3 can use the desmoglein-2 (DSG2) and CD46 receptors on susceptible cells. DSG2 was nearly absent in A2780 cells but was expressed in more than 90% of OAW42, OVCAR3, and OV-90 cells. After 96?hours, ONCOS-102 treatment showed significant oncolytic activity (?50%) in OAW42, OVCAR3, and OV-90 cells, but minimal activity in A2780 cells, suggesting DSG2 as the dominant receptor for ONCOS-102. Furthermore, retrospective analyses of phase I clinical trial of ONCOS-102 treatment of 12 patients with varied tumors indicated a correlation between viral genomes in blood and DSG2 RNA expression. These data support the role of DSG2 expression on cancer cells in virus infectivity and the continued development of ONCOS-102 for ovarian cancer treatment.

SUBMITTER: Kuryk L 

PROVIDER: S-EPMC7496614 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature