METHOD TO IMPROVE EFFICACY OF ADENOVIRAL VECTORS FOR GENE THERAPY

Adenoviral vectors have been extensively used to transfer genes into mammalian cells due to their wide spectrum of tissue specificity and their efficient delivery. However, variable transduction efficiency in vivo remains a major hurdle for effective clinical application of adenoviral vectors for gene therapy. Efficient adenoviral vector-mediated gene transfer depends on the presence of adequate levels of the coxsackie-adenovirus receptor (CAR) on the surface of target cells, which is necessary for the receptor-mediated endocytosis of the vector. Several tumor cells express relatively low levels of CAR receptors, e.g. head and neck carcinoma, GI cancers, melanomas, urological tumors and gliomas, thus limiting the efficiency of adenoviral-mediated gene therapy.

In order to optimize the adenoviral transduction, UCSF investigators have discovered a novel strategy to upregulate CAR receptor expression on tumor cells by modulating a cellular signal transduction pathway. Treatment of cancer cell lines with specific inhibitors of this signal transduction pathway leads to significantly increased CAR protein levels as well as increased adenoviral uptake.

Co-administration of inhibitors of this signal transduction pathway, such as antibodies, antisense or small molecules, with the therapeutic adenoviral vector may be a simple way of increasing the efficiency of adenoviral-mediated gene transfer to cells that are otherwise poorly transduced due to a lack of a sufficient number of CAR receptors on their surface.

If you would like to receive further information about this technology and potential licensing opportunities, please contact:

Sunita Rajdev, Ph.D.
Licensing Officer
(415) 353-4470 phone
(415) 348-1579 fax
Sunita Rajdev

Reference: OTM Case #SF01-101