title: Species D human adenovirus type 9 exhibits better virus-spread ability for antitumor efficacy among alternative serotypes.
abstract: Species C human adenovirus serotype 5 (HAdV-C5) is widely used as a vector for cancer gene therapy, because it efficiently transduces target cells. A variety of HAdV-C5 vectors have been developed and tested in vitro and in vivo for cancer gene therapy. While clinical trials with HAdV-C5 vectors resulted in effective responses in many cancer patients, administration of HAdV-C5 vectors to solid tumors showed responses in a limited area. A biological barrier in tumor mass is considered to hinder viral spread of HAdV-C5 vectors from infected cells. Therefore, efficient virus-spread from an infected tumor cell to surrounding tumor cells is required for successful cancer gene therapy. In this study, we compared HAdV-C5 to sixteen other HAdV serotypes selected from species A to G for virus-spread ability in vitro. HAdV-D9 showed better virus-spread ability than other serotypes, and its viral progeny were efficiently released from infected cells during viral replication. Although the HAdV-D9 fiber protein contains a binding site for coxsackie B virus and adenovirus receptor (CAR), HAdV-D9 showed expanded tropism for infection due to human CAR (hCAR)-independent attachment to target cells. HAdV-D9 infection effectively killed hCAR-negative cancer cells as well as hCAR-positive cancer cells. These results suggest that HADV-D9, with its better virus-spread ability, could have improved therapeutic efficacy in solid tumors compared to HAdV-C5.
authors: Cancer Biology Division, School of Medicine, Washington University in St. Louis, St. Louis, Missouri, United States of America.
authors: Junji
authors: J
authors: Uchino
authors: Cancer Biology Division, School of Medicine, Washington University in St. Louis, St. Louis, Missouri, United States of America ; Biologic Therapeutics Center, Department of Radiation Oncology, School of Medicine, Washington University in St. Louis, St. Louis, Missouri, United States of America.
authors: David T
authors: DT
authors: Curiel
authors: Cancer Biology Division, School of Medicine, Washington University in St. Louis, St. Louis, Missouri, United States of America.
authors: Hideyo
authors: H
authors: Ugai
mesh_terms: D000258:Adenovirus Infections, Human / Q000473:pathology / Q000821:virology; D000260:Adenoviruses, Human / Q000145:classification* / Q000187:drug effects / Q000502:physiology*; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D016923:Cell Death / Q000187:drug effects; D002460:Cell Line; D062727:Coxsackie and Adenovirus Receptor-Like Membrane Protein / Q000378:metabolism; D003470:Culture Media; D006801:Humans; D012703:Serotyping; D013045:Species Specificity; D018874:Spheroids, Cellular / Q000187:drug effects / Q000473:pathology; D019562:Viral Load / Q000187:drug effects
chemical_list: D000970:Antineoplastic Agents; D062727:Coxsackie and Adenovirus Receptor-Like Membrane Protein; D003470:Culture Media