Evaluation of E1-mutant adenoviruses as conditionally replicating agents for cancer therapy.
The oncolytic effect of adenoviruses may provide an efficient means to destroy tumor tissue if viruses could be developed with sufficient selectivity and efficacy. In this report we have characterized several adenoviruses, each with different mutations in the E1 region, for selective cytopathic effect in tumor cells in vitro and for their ability to inhibit tumor growth in vivo. Of the E1 mutants tested, we have identified one, E1Adl01/07, which preferentially induces cytopathic effects in a range of tumor cells versus primary cells. In addition, E1Adl01/07 significantly inhibited tumor growth and increased survival of mice in several models of human cancer. These results suggest that E1Adl01/07 might serve as an effective cancer therapeutic, combining both selectivity and efficacy.
Howe
J A
JA
Canji Incorporated, 3525 John Hopkins Court, San Diego, California 92121, USA. john.howe@canji.com
Demers
G W
GW
Johnson
D E
DE
Neugebauer
S E
SE
Perry
S T
ST
Vaillancourt
M T
MT
Faha
B
B
D000256:Adenoviridae / Q000235:genetics* / Q000502:physiology; D017500:Adenovirus E1A Proteins / Q000235:genetics / Q000627:therapeutic use*; D000818:Animals; D002460:Cell Line; D003588:Cytopathogenic Effect, Viral; D003673:Defective Viruses / Q000235:genetics / Q000502:physiology; D005260:Female; D015316:Genetic Therapy; D006801:Humans; D007275:Injections, Intravenous; D007279:Injections, Subcutaneous; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009154:Mutation; D009369:Neoplasms / Q000628:therapy*; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays
D017500:Adenovirus E1A Proteins