Targeted gene delivery to Kaposi's sarcoma cells via the fibroblast growth factor receptor. NLM AIDSLINE Important note: Information in this article was accurate in 1997. The state of the art may have changed since the publication date.

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Targeted gene delivery to Kaposi's sarcoma cells via the fibroblast growth factor receptor.

Cancer Res. 1997 Apr 15;57(8):1447-51. Unique Identifier : AIDSLINE MED/97262030
Goldman CK; Rogers BE; Douglas JT; Sosnowski BA; Ying W; Siegal GP; Baird A; Campain JA; Curiel DT; Gene Therapy Program, University of Alabama at Birmingham, 35294, USA.

Abstract: Kaposi's sarcoma (KS) is a major AIDS-related malignancy associated with significant morbidity and mortality. Current chemotherapeutic regimens are associated with a dismal prognosis. In an effort to develop a new approach to KS treatment, we devised a gene therapy-based adenovirus retargeting schema that redirects the adenovirus to fibroblast growth factor receptors endogenously present on the cell surface of KS cells. By using a bifunctional conjugate consisting of a blocking antiadenoviral knob Fab linked to basic fibroblast growth factor, FGF2, the gene transduction of KS cells was enhanced 7.7-44 fold; recombinant adenoviruses encoding either the firefly luciferase reporter gene, or the herpes simplex thymidine kinase gene, demonstrated quantitative enhancement of expression in the KS cell lines. In this regard, two KS cell lines that were previously refractory to native adenovirus transduction could be successfully transduced by the addition of the conjugate. This study thus addresses the utility of adenoviral retargeting to the FGF receptor in KS cells that are ordinarily transduction refractory to standardized approaches and allows practical development of gene therapy approaches for the treatment of human KS.
Keywords: *Acquired Immunodeficiency Syndrome/COMPLICATIONS *Adenoviridae/GENETICS *Gene Therapy *Genetic Vectors/THERAPEUTIC USE *Immunoglobulins, Fab/METABOLISM *Receptors, Fibroblast Growth Factor/METABOLISM *Sarcoma, Kaposi's/THERAPY *Transfection/METHODSKWDacquiredimmunodeficiencysyndrome/complicationsKWDadenoviridae/geneticsKWDgenetherapyKWDgeneticvectors/therapeuticuseKWDimmunoglobulins,fab/metabolismKWDreceptors,fibroblastgrowthfactor/metabolismKWDsarcoma,kaposi's/therapyKWDtransfection/methods
970730
M9772105

Copyright © 1997 - National Library of Medicine. Reproduced under license with the National Library of Medicine, Bethesda, MD.

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