Modulation of coxsackie-adenovirus receptor expression for increased adenoviral transgene expression.
An important determinant of gene transfer efficacy with adenoviral vectors is expression of the primary receptor, the coxsackie-adenovirus receptor. Unfortunately, expression may often be low in advanced clinical cancers, including ovarian, colorectal, lung, prostate, and breast cancer. In this study we investigated the feasibility of increasing transgene expression by incubating ovarian cancer cells with various agents and then performing transgene expression analysis. Fluorescence-activated cell sorting and quantitative reverse transcription-PCR were subsequently performed for correlation with receptor and mRNA up-regulation. Furthermore, the results were confirmed in purified clinical ovarian cancer specimens. Possible clinical application was tested using i.p. administration in an orthotopic ovarian cancer animal model. This approach could be useful for increasing adenoviral transgene expression in the context of clinical trials.
Hemminki
Akseli
A
Division of Human Gene Therapy, Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama 35294, USA. Akseli.Femminki@Helsinki.Fi
Kanerva
Anna
A
Liu
Bin
B
Wang
Minghui
M
Alvarez
Ronald D
RD
Siegal
Gene P
GP
Curiel
David T
DT
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D003131:Combined Modality Therapy; D062727:Coxsackie and Adenovirus Receptor-Like Membrane Protein; D005260:Female; D005434:Flow Cytometry; D015870:Gene Expression / Q000187:drug effects; D015316:Genetic Therapy / Q000379:methods*; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D010051:Ovarian Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000628:therapy / Q000821:virology; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D011991:Receptors, Virus / Q000096:biosynthesis* / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019076:Transgenes / Q000187:drug effects*; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays
D000970:Antineoplastic Agents; C568771:CLMP protein, human; C568772:CLMP protein, mouse; D062727:Coxsackie and Adenovirus Receptor-Like Membrane Protein; D012333:RNA, Messenger; D011991:Receptors, Virus