Rabbit antibodies are a popular choice for therapeutic antibody discovery, due to their high affinity and specificity for antigens. However, the process of antibody production from rabbits is often time consuming and expensive. To overcome this, several new technologies have been developed that facilitate rabbit monoclonal antibody production to accelerate the development of new therapeutic antibodies.
Custom stem cell treatments starts with immunization of 2 to 10 New Zealand White rabbits with the desired antigen. After a suitable antigen titer is obtained, the rabbits are put on a production bleed collection cycle. This cycle is typically repeated until sufficient antibody titers are obtained to start the characterization and recombinant expression processes.
Several methods have been used to isolate antigen-specific rabbit memory B cells or plasma cells from peripheral blood to generate functional mAbs. Some of the most popular platforms combine FACS or manual micromanipulation with phage cloning to achieve this (11, 12, 15). These technology platforms generate recombinant mAbs through the covalent attachment of mAb heavy and light chains via their variable domains, which are linked by a flexible hinge region with three disulfide bonds.
Tissue-Based Diagnostic Tools: Enhancing Precision in Clinical and Research Settings
In addition, several other technologies have been utilized to humanize rabbit antibodies with a high degree of success (16, 17, 19). For example, antibody phage display has been a very successful platform for humanizing rabbit antibodies with highly diverse CDRs, and the resulting humanized antibodies retain excellent binding properties for their target antigens (20). However, these techniques are time-consuming and labor intensive and therefore limit the number of rabbit mAbs that can be produced per year.