What You Must Know About Antibody Engineering

Along with information technology, biotechnology is the greatest motivator for global economic development in the 21st century. It is maturing into the leading technology that may reshape the pattern of future industry as well as economy. Following up biotechnology’s continuously building itself, antibody engineering, the main force of biotechnology industrialization, has earned itself an important place in this field, bio-pharmacy in particular.

Antibody engineering encompasses discovery methods, production strategies and modification techniques that have brought forward clinically investigated and marketed therapeutics. Among them, IgG construction, antibody stability improvement and scFv/Fab construction are the three that antibody engineers focused much of their efforts on.

IgG Construction

To mimic the behavior of a recombinant human IgG antibody targeting a human protein in humans the best, specificity-matching recombinant mouse IgG antibodies derived from phage display and mouse scFv/Fab libraries targeting mouse proteins are frequently produced and used in animal models.

Creative Biolabs uses a modified FRT/Flp-In recombinase system to produce human IgG in CHO cells for stable expression of humanized/recombinant human IgG. The same approach is used in stable expression of recombinant mouse IgG. They have pre-selected CHO cell lines that contain a single stably integrated FRT site at a transcriptionally active genomic locus. It has been proved that these locus can produce high level expressers of recombinant human IgGs targeting various antigens. Unfortunately, even starting from these pre-selected cell lines, significant amount of time and effort are required to create a stable cell line that can express recombinant human or mouse IgG at a cost-effective level, 800mg/Lm, for instance.

Antibody Stability Improvement

With the consistent growth of therapeutic antibodies in global market, many efforts have been made to improve the engineering technologies, safety and efficacy of therapeutic antibodies, among which stability is one of the most important functional requirements for the use of antibodies in therapeutic and diagnostic applications. Also, there are many institutions and groups are working on antibody stability improvement, such as Creative Biolabs and Abcam.

scFv/Fab Construction

Generally, there are three routes to have a scFv or Fab target a specific antigen. The first is to generate a mouse hybridoma clone, then convert full IgG or IgM into a scFv or Fab. The second approach is to create an immunized phage display scFv or Fab mouse library, then use the antigen to screen the library. The third one is to use the antigen to screen a premade scFv or Fab antibody phage display library, usually a human one, to get scFv or Fab clones directly. Besides, Creative Biolabs are also able to convert chicken IgY into scFv or Fab fragments.

Although we humans now have already learned much about antibody engineering, there are still more remained unexplored.