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In a phase II/III clinical trial intraperitoneal (i.p.) administration of a group C adenovirus vector (Ad5) caused bowel adhesion formation, perforation and obstruction. However, we had found that i.p. group B, in contrast to group C adenoviruses, did not cause adhesions in nude BALB/c ovarian cancer models, prompting further investigation. Ex vivo, group B Ad11 caused lower inflammatory responses than Ad5 on BALB/c peritoneal macrophages. In vivo, i.p. Ad11 triggered short-term cytokine and cellular responses equal to Ad5 in both human CD46-positive and -negative mice. In contrast, in a long-term study of repeated i.p. administration, Ad11 caused no/mild, whereas Ad5 induced moderate/severe adhesions and substantial liver toxicity accompanied by elevated levels of IFNγ and VEGF and loss of i.p. macrophages, regardless of CD46 expression. It appears that, although i.p. Ad11 evokes immediate inflammation similar to Ad5, repeated administration of Ad11 is better tolerated and long-term fibrotic tissue remodelling is reduced.

Original publication

DOI

10.1016/j.virol.2013.08.032

Type

Journal article

Journal

Virology

Publication Date

12/2013

Volume

447

Pages

74 - 83

Keywords

Ad11, Ad5, Adenovirus, CD46-transgenic mice, Gene therapy, Intraperitoneal inflammation, Ovarian cancer, Virotherapy, Adenoviruses, Human, Animals, Cell Line, Disease Models, Animal, Drug Carriers, Female, Genetic Therapy, Genetic Vectors, Humans, Intraabdominal Infections, Mice, Ovarian Neoplasms