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

Area of Science:

• Oncology
• Molecular Biology
• Immunology

Background:

• Immunotoxins are engineered proteins for targeted cancer therapy, combining antibody fragments with toxins.
• Current immunotoxins face challenges like immunogenicity and neutralizing antibody development, limiting patient response.
• ROR1 is a target antigen expressed on certain cancer cells, making it a candidate for targeted therapy.

Purpose of the Study:

• To propose and evaluate a novel immunotoxin, anti ROR1 single chain fragment variable antibody (scFv)-endonuclease G (EndoG), for targeted cancer therapy.
• To assess the structural integrity and stability of the anti ROR1 scFv-EndoG construct.
• To explore the potential of scFv-EndoG constructs as a new class of cancer therapeutics.

Main Methods:

• Three-dimensional structural modeling of the anti ROR1 scFv-EndoG protein.
• Utilizing structure validation tools to confirm model accuracy and reliability.
• Employing molecular dynamic (MD) simulations to assess protein model stability and integrity.

Main Results:

• Structural modeling and validation confirmed the anti ROR1 scFv-EndoG protein model to be of acceptable and good quality.
• Molecular dynamic simulations indicated favorable stability and integrity of the proposed protein structure.
• The scFv portion is predicted to bind the ROR1 extracellular domain, facilitating toxin delivery.

Conclusions:

• The anti ROR1 scFv-EndoG construct is a promising candidate for targeted therapy of ROR1-expressing cancers.
• This immunotoxin is designed to deliver non-immunogenic human endonuclease G into cancer cells, inducing apoptosis.
• Anti-tumor antigen scFv-EndoG formats represent a potentially valuable therapeutic strategy for cancer treatment.