A Modified Adenovirus Vector-Mediated Antibody Screening Method Identifies EphA2 as a Cancer Target

Translational Oncology
Toshihiro TanakaYasushi Takamatsu

Abstract

We constructed a genetically modified adenovirus vector incorporating an IgG Fc-binding motif from staphylococcal protein A, Z33 (Adv-FZ33). Adv-FZ33 allows an antibody to redirect the vector to a target molecule on the cell surface. We attempted to search for target antigen candidates and antibodies that allowed highly selective gene transduction into malignant tumors. Hybridoma libraries producing monoclonal antibodies (mAbs) were screened that increased transduction efficiency in cancer cell lines after cross-linking with Adv-FZ33. Target antigens of the mAbs were identified by immunoprecipitation and mass spectrometry. Of these mAbs, we noted a clone, F2-27, that recognized the receptor tyrosine kinase EphA2. Next, we generated an adenovirus vector, Ax3CMTK-FZ33, that expressed a herpes simplex virus thymidine kinase (HSV-TK). The therapeutic efficacy of F2-27-mediated HSV-TK gene transduction, followed by ganciclovir (GCV) administration, was studied in vitro. The inhibitory effect of F2-27 on cancer cell invasion was investigated by a three-dimensional spheroid formation assay. In vitro reporter gene expression after Adv-FZ33 infection via F2-27 was 146 times higher than with control mAb in EphA2-expressing cancer cell li...Continue Reading

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Citations

Sep 30, 2017·Frontiers in Immunology·Kristina M IlievaSophia N Karagiannis

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Methods Mentioned

BETA
flow cytometry
FACS
transfection
Fluorescence microscopy
enzyme-linked immunosorbent assays
transfect
gene transfer

Software Mentioned

ImageJ

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