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

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.