Pharmacological evaluation of bioconjugated Trastuzumab using the AbYlinkTM regio-selective conjugation technology in gastric cancer expressing HER2+
Autors:
Céline Mothes, Peggy Provent, Marie Ruch, Mathieu Moreau, Michael Claron, Alex Helbling, Viktoriia Postupalenko, Léo Marx, PatrickGarrouste, Eftychia Koumarianou
Oncodesign Services, Dijon Cedex, France, ICMUB, CGFL, Debiopharm Research & Manufacturing
Abstract :
Purpose/introduction
Bioconjugation is a critical step in the development of Antibody Drug Conjugates with two main strategies dominating the field. One approach employs covalent chemistry to randomly bind a drug to the accessible Lysines or Cysteines on an antibody. The other strategy is site-specific, using covalent chemistry to bind a drug ligand at defined amino acid positions within the antibody. AbYlinkTM is a novel regio-selective labeling method for antibodies, enabling a single-step covalent conjugation of payloads such as radionuclide chelators to the Fc domain of an antibody. Given the selectivity of this reaction for the Fc region of the immunoglobulin, the affinity of the antibody to the antigen isn’t compromised, unlike randomly labelled antibodies. The chelators that are covalently attached to the antibody enable radiolabeling with radioisotopes such as Gallium-68, Lutetium-177 and Indium-111 for molecular radiotherapy or molecular imaging purposes.
Conclusion
We have successfully validated in vivo the use of AbYlink™ technology in the context of Antibody Radio Conjugates. This regio-selective bioconjugation strategy holdspotential for wider application across molecular radiotherapies or pharmacodynamic assessment of antibodies.
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