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7th Annual US Bioassay Conference Seattle (WA)14-16 Marzo 2023 and BEBPA’s Hybrid European Bioassay Conference Roma, 27-29 Settembre 2022

Combination of SPR-based binding kinetic and SEC-based conformational assay to evaluate mAb-target antigen physicochemical properties important for ADCs therapeutic function

Alessandra Mariani, Sabrina Novelli, Meri Gabrielli and Thoralf Keller

CD205/Ly75, was selected as target antigen for a humanized anti-CD205 IgG1 conjugated to the DM4  toxin, MEN1309. The over expression of CD205 in different solid cancers, combined with its  capability to induce ligand internalization, were key factors in the election of CD205 to excellent target for  an Antibody Drug Conjugate (ADC). On the other side, the CD205 physiological expression on  Antigen Presenting Cells (APCs) and leucocytes, represents a risk factor for toxic side effect induced by  MEN1309 binding on healthy blood cells, a phenomenon frequent for ADCs and known as ”on-target but  off-tumor” binding.  

In the present study, the pH dependent CD205 conformational change  impact on the binding of MEN1309 was evaluated, looking for possible consequences on MEN1309 therapeutic function.  

The combination between SPR-based binding kinetic and SEC-based conformational assays allows  to evaluate mAb-target antigen physiochemical properties which could enhance the selectivity of ADCs for  the malignant cells.