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

Toshihiro Tanaka1, Hiromi Yamada2, Masahide Kuroki2

  • 1Division of Oncology, Hematology and Infectious Diseases, Department of Internal Medicine, Fukuoka University, ​7-45-1 Nanakuma, Jonan-ku, Fukuoka, 814-0180, Japan.

Translational Oncology
|May 16, 2017
PubMed
Summary
This summary is machine-generated.

A novel adenovirus vector (Adv-FZ33) targets cancer cells using antibodies. This system, exemplified by the F2-27 antibody targeting EphA2, enables selective gene therapy and inhibits cancer cell invasion.

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Area of Science:

  • Oncolytic virology
  • Molecular and cellular oncology
  • Immunotherapy

Background:

  • Genetically modified adenovirus vector (Adv-FZ33) developed with a staphylococcal protein A motif.
  • Adv-FZ33 facilitates antibody-mediated targeting of cell surface molecules for gene delivery.
  • Objective to identify target antigens and antibodies for selective gene transduction into tumors.

Purpose of the Study:

  • To develop a targeted gene therapy system for cancer.
  • To identify specific antibodies and antigens for enhanced adenovirus-mediated gene delivery.
  • To evaluate the therapeutic potential of antibody-guided gene transduction and its effect on cancer cell behavior.

Main Methods:

  • Screening hybridoma libraries for monoclonal antibodies (mAbs) enhancing Adv-FZ33 transduction.
  • Identifying target antigens using immunoprecipitation and mass spectrometry.
  • Generating an adenovirus vector (Ax3CMTK-FZ33) expressing herpes simplex virus thymidine kinase (HSV-TK) for targeted therapy.

Main Results:

  • The F2-27 mAb targeting EphA2 significantly enhanced reporter gene expression (146-fold increase).
  • F2-27-mediated delivery of HSV-TK gene resulted in potent, ganciclovir-dependent cancer cell cytotoxicity.
  • F2-27 demonstrated independent inhibition of EphA2-positive breast cancer cell migration in 3D culture.

Conclusions:

  • The modified adenovirus and hybridoma screening approach is effective for targeted cancer therapy development.
  • The F2-27 antibody shows promise as an antibody-based therapeutic for EphA2-positive cancers.
  • This strategy offers a platform for developing novel antibody-guided gene therapies for various malignancies.