What You Should Know About Single Domain Antibody

Candy Swift
Jul 20, 2017 · 2 min read

Antibody drugs are one of the fastest growing biotech drugs in recent years, taking up 1/3 of total sales of biotech drugs. Their sources have been developing from mouse-derived antibodies at early stage to humanization and whole human antibodies, which greatly reduces the side effects brought by antibody drugs’ heterogeneity in multiple clinical applications.

Heavy chain antibody is a naturally missing light chain found in camel by Hamers-Casterman and several scientists in 1993. It consists of only antibodies of with heavy chains, so that it is named heavy chain antibodies. The heavy chain variable region fragment of the antibody, i.e., the heavy chain single domain antibody, can directly recognize the antigenic epitope and is the smallest molecular weight antibody fragment with antigenic function found so far. Therefore, it is also called nanoantibody.

It was found that the heavy chain antibody has a small molecular weight and was easy to express compared to conventional antibody. Meanwhile, it has a longer CDR3 region and generally has 16 to 20 amino acid residues, which showed higher specificity when recognizing the epitope affinity, and can identify unique epitopes of antigenic epitopes.

Moreover, it is characterized by high solubility and stability compared with traditional antibody. In addition, the unique physical and chemical characteristics of heavy chain antibodies also make this type of antibody stand out in the diagnosis area. Therefore, the development of heavy chain antibody with specific target molecule has become a new strategy for the preparation of antibody in recent years.

Ablynx is one of the typical representatives of the companies that are currently developing heavy chain antibody drugs involving cardiovascular disease, cancer and autoimmune diseases. There are many small and medium-sized biotech companies that have made and are making contributes to this area, such as Creative Biolabs.

Phage display antibody library is one of the most prominent advances in antibody engineering in recent years. The technology mainly exhibits antibody molecules on the phage surface and uses targeted antigen molecules to express specific antibody molecules. Expresses antibody and identify its functions through genetic engineering, so as to obtain functional antibody molecules.

Once the relevant antibody library has been constructed, a variety of screening strategies (such as solid, liquid or cell screening) can be used to screen specific antibodies. On the one hand, it avoids animal immunization, the long lasting boring work. On the other hand, depending on the screening device, a high throughput screening of the antibody can be achieved to a certain extent, thereby shortening the preparation cycle of the antibody. In addition, for some toxic or immunogenic targets, phage antibody library technique can also be used to achieve the screening of specific antibodies, showing its unique technical advantages.

Combining the advantages of heavy chain antibody and phage display antibody library, large capacity non-immune alpaca heavy chain single domain phage antibody library can be established to complete the identification of antibody library, laying the foundation for the screening of specific heavy chain antibodies.

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