Enhanced therapeutic efficacy for XXXX with a serotype 3 receptor-targeted oncolytic adenovirus.

@entity43 @entity1 @entity137 @entity11650 @entity5 @entity39125 @entity189 @entity16565
Oncolytic viruses that are replication competent in @entity5 but not in normal cells represent a novel approach for treating @entity5 . However, the oncolytic potency of replicating agents is determined directly by their capability of infecting target cells. Most adenoviruses used for gene therapy or virotherapy have been based on serotype 5 ( @entity11650 ). Unfortunately, expression of the primary receptor for @entity11650 (the coxsackie-adenovirus receptor, or @entity16565 ) is highly variable on ovarian and other @entity5 cells. By performing genetic fiber pseudotyping, we created @entity11650 /3- @entity39125 , a conditionally replicating adenovirus that does not bind @entity16565 but facilitates entry into and killing of @entity43 cells. We show replication of @entity11650 /3- @entity39125 and subsequent oncolysis of @entity43 lines. Replication was also analyzed with quantitative PCR on three-dimensional primary @entity5 cell spheroids purified from @entity1 samples. Moreover, in a therapeutic orthotopic model of peritoneal @entity189 , dramatically enhanced survival was noted. Finally, @entity11650 /3- @entity39125 achieved a significant antitumor effect as assessed by noninvasive, in vivo bioluminescence imaging. Therefore, the preclinical therapeutic efficacy of @entity11650 /3- @entity39125 is improved over the respective @entity16565 - and integrin-binding controls. Taken together with promising biodistribution and @entity137 data, this approach could translate into successful clinical interventions for @entity43 @entity1 .
