Anti-ROR1 scFv-EndoG as a Novel Anti-Cancer Therapeutic Drug

Document Type: Research Articles

Authors

1 Department of immunology, Shiraz University of Medical Sciences, Shiraz, Iran

2 Applied Biotechnology Research Center, Baqiyatallah University of Medical Sciences, Tehran, Iran.

3 Faculty Member of Production and Research Complex, Pasteur Institute of Iran, Tehran, Iran.

Abstract

 
Aim: Immunotoxins are proteins that consist of an antibody fragment linked to a toxin, used as agents for targeted therapy of cancers. Although the most potent immunotoxins are made from bacterial and plant toxins, obstacles which contribute to poor responses are immunogenicity in patients and rapid development of neutralizing antibodies. In the present study we proposed a new therapeutic immunotoxin for targeted cancer therapy of ROR1 expressing cancers: an anti ROR1 single chain fragment variable antibody (scFv)-endonuclease G (anti ROR1 scFv-EndoG). Methods: The three-dimensional structure of anti ROR1 scFv-EndoG protein was modeled and structure validation tools were employed to confirm the accuracy and reliability of the developed model. In addition, stability and integrity of the model were assessed by molecular dynamic (MD) simulation. Results: All results suggested the protein model to be acceptable and of good quality. Conclusions: Anti-ROR1 scFv-EndoG would be expected to bind to the ROR1 extracellular domain by its scFv portion and selectively deliver non-immunogenic human endonuclease G enzyme as an end-stage apoptosis molecule into ROR1-expressing cancer cells and lead rapidly to apoptosis. We believe that anti ROR1 and other anti-tumor antigen scFv-EndoG forms may be helpful for cancer therapy.

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