How Camels Change the Antibody Engineering Industry?

In the late 1980s, researchers in a lab in Brussels found some old camel blood at the back of a freezer when extracting antibodies from human blood samples. Then, it was noticed that in addition to normal antibodies, some smaller antibodies devoid of light chains were extracted from the camel blood. Moreover, the heavy chains of these small antibodies were shorter and have only three domains, which lack the domain that binds the heavy chains to the light chains. This is how camelid antibodies came into sight by accident, which later proven to be a revolutionary finding for antibody engineering.

These smaller camel antibodies, now named nanobodies or VHHs, are derived from the Camelidae family of mammals such as the llamas, camels, and alpacas and now have been widely used as a research tool in different scientific and therapeutic fields.

Advantages of Camelid Antibodies

Compared to conventional antibodies, the most obvious superiority of camelid antibodies is their small size, which allows more new properties to be accessed by genetic engineering. The property of small size grants nanobodies an impressive penetration rate into tissues and low immunogenicity, making them promising therapeutics as a drug is anticipated to be attached to the antibodies and delivered directly to the problematic tissues.

The smaller size of camelid antibodies also means more easy removal from the bloodstream. This property can be applied to antibody engineering for toxin binding, which enables a rapid toxin removal from the bloodstream and significant reduction of treatment side effects. Moreover, camelid antibodies have a relatively shorter half-life, which is helpful for tumor imaging on diseased tissues requiring rapid clearance in a short time.

Small antibodies also offer the potential to target brain tumors. Currently, 98% of small molecule drugs cannot pass the blood-brain barrier—the wall that prevents potentially harmful substances circulating in the blood from entering the brain1. Regular antibodies are also too large to pass the barrier, but nanobodies have the potential to pass, and possibly deliver drugs to target tumors.

Biopharmaceutical company Ablynx is currently leading the development of nanobodies. Their FDA approved nanobody Ozoralizmab is in its phase-II clinical trial. It works by neutralizing the inflammatory response by masking a protein called TNFα in joints associated with rheumatoid arthritis. This debilitating disorder affects 1% of the world’s population, causing chronic and progressive joint inflammation. Patients in the trial saw around a 70% reduction in joint swelling after a 12-week treatment course.

In terms of targeting specificity, high thermostability, and good solubility, camelid antibodies have been widely applied in a number of preclinical and clinical studies, such as using camelid antibodies as imaging reagents, therapeutics against different diseases, and radiolabeling signs.

Production and Manufacture of Camelid Antibodies

Considering the broad application prospects in different research fields, a swath of antibodies with novel structures and functions targeting different molecules have been developed and engineered based upon camelid single chain antibodies.

Functional antibodies usually are produced in mammalian cells, for which researchers would immunize Llama or Alpaca to get unpurified blood samples containing both normal and heavy-chain only antibodies. After lymphocytes isolation and mRNA extraction, the screening and purification of camelid antibodies are performed to produce monoclonal VHHs with high affinity. VHHs can be economically produced on a large scale in microbial production systems, including Escherichia coli (E. coli), filamentous fungi, and yeasts.

Antibody therapy is on the rise and getting more and more complex and promising with the emergence of recombinant DNA technology. Leveraging the genetic engineering technology, camelid VHHs with multiple advantages are considered as one of the most promising candidates for novel therapies against a wide number of cancers, autoimmune diseases, and pathogens. No one had ever expected that all these amazing possibilities started from an accidental discovery of some frozen camel blood.