Triple vector for discovery of antibody molecules in full therapeutic format

Triple vector for discovery of antibody molecules in full therapeutic format


Phage display technology is a very powerful tool widely used to select antibody fragments such as Fabs, scFvs and VHHs.
When envisioned for, mainly, therapeutic purposes the phage display selected antibody fragments are converted to immunoglobulins or to Fc fusion proteins and expressed in mammalian cells. The resulting final molecules are bivalent, possess Fc effector function and a half-life comparable to natural immunoglobulins.
This conversion process is a bottleneck in antibody discovery as this is labor intensive and time-consuming. Moreover, for some antibody fragments (i.e. scFvs) the conversion to Fc fusion proteins result in loss of activity.
To circumvent all these drawbacks, we have generated a vector (“triple vector”) containing the elements necessary not only for phage display and the production of soluble antibody fragments fused to human Fc in bacteria, but also for production in mammalian cells. Ultimately the selection of immunological effector function bearing bivalent molecules, bypassing the cloning into mammalian expression vectors, will accelerate the drug discovery process.
The selection of anti-human CXCR4 VHH-human Fc molecules from naïve repertoires using the generated triple vector is shown as case study under the “Case Studies” section.