Inter-patient variation in efficacy of five oncolytic adenovirus candidates for ovarian cancer therapy

Autor: Akseli Hemminki, Masato Yamamoto, Koichi Takayama, Gerd J. Bauerschmitz, Kaori Suzuki, David T. Curiel, Anna Kanerva, Minghui Wang, Bin Liu, Snehal M. Bhoola, John T. Lam, Ronald D. Alvarez, Gene P. Siegal, Mack N. Barnes
Rok vydání: 2004
Předmět:
Vascular Endothelial Growth Factor A
Oncolytic adenovirus
Genetic enhancement
Genetic Vectors
Cell
Adenocarcinoma
Biology
Virus Replication
Polymerase Chain Reaction
Adenoviridae
Mice
03 medical and health sciences
0302 clinical medicine
Spheroids
Cellular
Drug Discovery
Tumor Cells
Cultured
Genetics
medicine
Animals
Humans
Neoplasm Metastasis
Promoter Regions
Genetic
Solid tumor
Molecular Biology
Genetics (clinical)
030304 developmental biology
Ovarian Neoplasms
0303 health sciences
Cell Death
Genetic Therapy
Neoplasms
Experimental
medicine.disease
Virology
3. Good health
Oncolytic virus
Cancer treatment
Treatment Outcome
Real-time polymerase chain reaction
medicine.anatomical_structure
Gene Expression Regulation
030220 oncology & carcinogenesis
DNA
Viral
Cancer research
Molecular Medicine
Female
Ovarian cancer
Zdroj: The Journal of Gene Medicine. 6:1333-1342
ISSN: 1521-2254
1099-498X
DOI: 10.1002/jgm.635
Popis: Gene therapy offers a new strategy for cancer treatment. Adenoviruses represent the most widely used gene therapy vector and feature an excellent safety record. Conditionally replicative adenoviruses (CRAds) effect solid tumor penetration and tumor selective oncolysis and consequently offer potential efficacy for metastatic disease treatment. We evaluated five CRAds as candidate clinical agents for ovarian cancer therapy: RGDCRADcox-2R, Ad5VEGFE1, Ad5/3VEGFE1, Ad5-Delta24RGD, and Ad5/3-Delta24.DNA replication by these five CRAds, wild-type adenovirus, and an E1-deleted control was measured in purified primary ovarian cancer cell spheroids by quantitative PCR. CRAd-mediated oncolysis was quantified in ovarian cancer cell monolayers and three-dimensional spheroids by cellular viability assays. The therapeutic efficacy of each CRAd was tested by intraperitoneal administration in mice with peritoneally disseminated human ovarian cancer.An increase in viral DNA was noted in primary tumor cell spheroids for all replicative viruses tested. Variation was noted in viral DNA replication between patient samples. All five CRAds induced remarkable oncolysis. They also prolonged survival in vivo compared with the wild-type control group.All five CRAds tested showed robust DNA replication, oncolysis, and in vivo therapeutic efficacy. Each virus has potential for clinical testing, and such further testing will ultimately determine its safety and relative usefulness. Variation of CRAd DNA replication between different patient samples suggests that target tissue features, such as surface receptors and endogenous transcription factors, may affect CRAd infectivity and replicativity. Evaluation of such factors may become important to optimize cancer therapy for individual patients.
Databáze: OpenAIRE
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