RESUMO
Monoclonal antibodies (mAbs) for therapeutic applications should be as similar to native human antibodies as possible to minimize their immunogenicity in patients. Several transgenic animal platforms are available for the generation of fully human mAbs. Attributes such as specificity, efficacy and Chemistry, Manufacturing and Controls (CMC) developability of antibodies against a specific target are typically established for antibodies obtained from one platform only. In this study, monoclonal antibodies (mAbs) cross-reactive against human and cynomolgus LAMP1 were derived from the human immunoglobulin transgenic TRIANNI mouse and OmniChicken® platforms and assessed for their specificity, sequence diversity, ability to bind to and internalize into tumor cells, expected immunogenicity and CMC developability. Our results show that the two platforms were complementary at providing a large diversity of mAbs with respect to epitope coverage and antibody sequence diversity. Furthermore, most antibodies originating from either platform exhibited good manufacturability characteristics.
Assuntos
Anticorpos Monoclonais/imunologia , Epitopos/imunologia , Proteínas de Membrana Lisossomal/imunologia , Animais , Animais Geneticamente Modificados , Anticorpos Monoclonais/química , Galinhas , Células HEK293 , Humanos , Imunização , Macaca fascicularis , Camundongos , Modelos MolecularesRESUMO
Therapeutic antibodies generation has to be faster with less development costs. This requires combination of in silico predictions associated with cutting edge screening and characterization technologies. Here, non-exhaustive examples illustrate this simultaneity need.
TITLE: Exemples d'études de développabilité apportant un éclairage à la prise de décision. ABSTRACT: De nos jours, la génération d'anticorps thérapeutiques doit être plus rapide avec des coûts de développement moins importants. Pour cela, des prédictions in silico sont associées à des technologies de criblage et de caractérisation de pointe. Les exemples choisis ici sont non-exhaustifs mais illustrent ce besoin de travailler en parallèle.
