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Abstract During the last few years Antibody-Drug Conjugates (ADCs) have become one of the most active and very promising therapeutic weapons. Lessons learned from the traditional chemical conjugations (via lysine or cysteine residues of the antibodies) and the clinical studies of the developed ADCs have recently paved the way to the improvement of the conjugation technologies. Use of site-specific conjugation is considered as the promising path for improving the design and development of homogeneous ADCs with controlled Drug-Antibody ratio (DAR). Moreover, some of these conjugations can be applied to antibody fragments such as Fab, scfv and VHH for which random and chemical conjugation showed significant limitations. In this study, we identified a novel small peptide substrate (Q-tag) with high affinity and specificity of bacterial transglutaminase which can be genetically fused to different formats of antibodies of interest for the development of enzymatic site-specific conjugation we named “CovIsolink” platform. We describe the synthesis of chemically defined drugs conjugation in which the site and stoichiometry of conjugation are controlled using a genetically encoded Q-tag peptide with specific amino acids which serves as a substrate of bacterial transglutaminase. This approach has enabled the generation of homogeneous conjugates with DAR 1,7 for full IgG and 0,8 drug ratio for Fab, scfv and VHH antibody fragments without the presence of significant amounts of unconjugated antibody and fragments. As a proof of concept, Q-tagged anti Her-2 (human IgG1 (Trastuzumab) and the corresponding fragments (Fab, scfv and VHH) were engineered and conjugated with different aminated-payloads. The corresponding Cov-ADCs were evaluated in series of in vitro and in vivo assays, demonstrating similar tumor cell killing potency as Trastuzumab emtansine (Kadcyla®) even with lower drug-to-antibody ratio (DAR).

Résumé : Face à un enseignement parcellaire de la compétence scripturale, les apprenants de français langue étrangère (FLE) recourent souvent à l’emploi des expressions figées. Des expressions toutes faites et surtout toutes prêtes pour pallier leurs difficultés ; des expressions qu’ils mémorisent et emploient dès que l’occasion se présente, sans prendre en considération les erreurs et les incohérences que cette pratique peut engendrer. Nous nous penchons dans le cadre du présent article sur cette pratique scripturale, d'abord en tant que stratégie d'évitement à laquelle les apprenants recourent pour parer à leurs difficultés, ensuite sur l'usage qui peut en être fait en didactique de l'écrit en vue d'améliorer la qualité textuelle des productions écrites. Nous présentons, à cet effet, les résultats d'une expérimentation menée auprès d’apprenants algériens de deuxième année moyenne. Mots-clés : productions écrites, expressions figées, apprenant, pratique scripturale, didactique de l'écrit.