Construction of macaque immune-libraries

Abstract

Rapidly after the clinical success of the first murine therapeutic antibody licensed in 1985 (muromomab-CD3), the first limits of the therapeutic use of antibodies deriving from hybridoma technology appeared. Indeed, the nonhuman nature of these therapeutic antibodies makes them immunogenic when administrated to patients, which develop anti-drug antibodies (ADA). If repeated drug-administrations are needed, the immune response will accelerate the elimination of the drug, leading to a therapeutic failure, or in the worst case to an anaphylactic reaction against the murine protein. Several antibody generations were then developed to obtain better-tolerated molecules: chimeric, humanized, and fully human antibodies. The first antibody generation is fully based on cellular technology (mice hybridoma technology), but the next generations are improved by molecular engineering. Immune antibody phage-display libraries are one successful approach to isolating such engineered antibodies. One strategy to isolate high-affinity and well-tolerated antibodies when no immunized patients are available is based on the phage-display-screening of immune libraries deriving from immunized nonhuman primates, which are phylogenetically close to humans. This chapter presents the strategy for the construction of macaque antibody immune-libraries.