Antibodies Overview
Antibody basics
Antibodies are defence molecules in our body, produced by specialized immune cells known as B lymphocytes or B-cells. Their normal function is to protect us from infections. When used as therapeutics, antibodies can target specifically selected disease proteins, enabling us to fight illnesses that our bodies would not normally produce antibodies against, e.g., cancer.
Schematic representation of an antibody molecule
Antibodies are proteins that have a characteristic Y-shaped structure. Each B-cell generated by the immune system produces antibodies with a specific and unique target binding section, resulting in a huge diversity of target binding specificity. This ensures that almost any antigen that enters the body will be recognised by an antibody. B lymphocytes can be immortalized, resulting in cell lines producing monoclonal antibodies with a defined binding specificity.
Therapeutic antibodies overview
Antibodies are the body’s own defence molecules against viruses and bacterial infections. Medicine has, for a long time, sought methods for the selection, development and production of antibodies in order to use them as therapeutic drugs.
A major obstacle was that antibodies developed in laboratory animals, like mice and rats, (known as xenogenic antibodies) cannot be used for the treatment of human diseases, because they are recognized by the human immune system as foreign, causing an unwanted immune response and making the therapeutic antibody ineffective.
The first generation of therapeutic antibodies were chimeric antibodies containing only the antigen binding domains (shown here in red) from non-human origin. However, these antibodies may still cause unwanted immunogenic reactions, as the non-humanized portions are recognized as foreign.
The next step in antibody development was achieved by the generation of humanized antibodies, which contained non-human specific antibody binding regions inserted into the framework of a human antibody. This minimized the risk of an unwanted immunogenic reaction but still could not fully remove it.
Currently most therapeutic antibodies in development are fully human, thereby eliminating unwanted immunogenic side effects from the immune system. Previously, the two main approaches for the production of fully human antibodies were:
- Phage display/pro-karyotic systems
- Transgenic animals
The phage display system enables the expression of antibody fragments in prokaryotic cells (bacteria), which are eventually expressed on the surface of bacteriophages, where they are subsequently screened for antigen (target) binding. In order to generate fully human antibodies by phage display the fragments that bind the target need to be re-engineered to full-length antibodies and expressed in mammalian cells.
The transgenic animal systems allow the antibodies to be raised in their natural (eukaryotic) environment and selected for biological and binding activities.
Market
Therapeutic antibodies represent the most successful class of biological-based drugs with unparalleled growth potential. During the last five years the global revenue growth of antibody therapeutics has consistently grown by more than 30% per annum, reaching sales of over US$ 25 billion by the end of 2007 and projected to grow to almost US$ 45 billion by 2012.
By 2006, eighteen antibodies had been approved by the regulatory authorities for the treatment of human disease, and their excellent efficacy versus side effect profile is revolutionizing the treatment of many chronic and severe diseases.
As more than 200 antibodies against a wide variety of targets, and for various diseases, are currently in development, it is expected that during the coming 5 to10 years a significant number of these new therapeutics will become available. Amongst these, fully human antibodies are in high demand compared to their rodent or part-rodent counterparts, as they are more compatible with the human immune system and are expected to cause the least severe side effects. Approximately 30 fully human antibodies have now passed the initial clinical proof of concept stage. To date, almost all fully human antibodies in clinical development and on the market are derived from the current gold standard technologies for therapeutic antibody development: phage display and transgenic mice.
4-Antibody’s proprietary 4mAb™ platform provides a novel, unique and proven method, combining the proven strengths of the gold standard technologies to develop new fully human antibodies, as well as to optimize the efficacy of existing antibody products.
As therapeutic applications for monoclonal antibodies become wider, many more companies seek to develop this promising type of medicine and the 4mAb™ platform offers them the opportunity to do this.