title: Relaxin-expressing, fiber chimeric oncolytic adenovirus prolongs survival of tumor-bearing mice.
abstract: Selective replication of oncolytic viruses in tumor cells provides a promising approach for the treatment of human cancers. One of the limitations observed with oncolytic viruses currently used in the treatment of solid tumors is the inefficient spread of virus throughout the tumor mass following intratumoral injection. Data are presented showing that oncolytic adenoviruses expressing the relaxin gene and containing an Ad5/Ad35 chimeric fiber showed significantly enhanced transduction and increased virus spread throughout the tumor when compared with non-relaxin-expressing, Ad5-based viruses. The increased spread of such viruses throughout tumors correlated well with improved antitumor efficacy and overall survival in two highly metastatic tumor models. Furthermore, nonreplicating viruses expressing relaxin did not increase metastases, suggesting that high level expression of relaxin will not enhance metastatic spread of tumors. In summary, the data show that relaxin may play a role in rearranging matrix components within tumors, which helps recombinant oncolytic adenoviruses to spread effectively throughout the tumor mass and thereby increase the extent of viral replication within the tumor. Expressing relaxin from Ad5/Ad35 fiber chimeric adenoviruses may prove a potent and novel approach to treating patients with cancer.
authors.affiliation: Cell Genesys, Inc., South San Francisco, California 94080, USA. shanthi.ganesh@cellgenesys.com
authors.forename: Shanthi
authors.initials: S
authors.lastname: Ganesh
authors.forename: Melissa
authors.initials: M
authors.lastname: Gonzalez Edick
authors.forename: Neeraja
authors.initials: N
authors.lastname: Idamakanti
authors.forename: Marina
authors.initials: M
authors.lastname: Abramova
authors.forename: Melinda
authors.initials: M
authors.lastname: Vanroey
authors.forename: Michael
authors.initials: M
authors.lastname: Robinson
authors.forename: Chae-Ok
authors.initials: CO
authors.lastname: Yun
authors.forename: Karin
authors.initials: K
authors.lastname: Jooss
mesh_terms: D000256:Adenoviridae / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D000818:Animals; D045744:Cell Line, Tumor; D003094:Collagen / Q000378:metabolism; D005260:Female; D005822:Genetic Vectors / Q000235:genetics; D006801:Humans; D008297:Male; D051379:Mice; D009362:Neoplasm Metastasis; D050130:Oncolytic Virotherapy / Q000379:methods*; D011471:Prostatic Neoplasms / Q000235:genetics / Q000628:therapy* / Q000821:virology; D012065:Relaxin / Q000096:biosynthesis* / Q000235:genetics; D014779:Virus Replication; D023041:Xenograft Model Antitumor Assays
chemical_list: D012065:Relaxin; D003094:Collagen