“Magic Bullets” – Their Time Is Now
Ever since the discovery of antibodies in the 1890s, scientists and physicians have dreamed of harnessing their exquisite specificity and using them as “magic bullets” to combat all types of infectious diseases and cancer. Many technical obstacles had to be overcome and new technologies had to be developed before this dream could become reality. One monumental milestone was the development of a method to make monoclonal antibodies (mAbs). These lab-developed proteins are produced by individual B cells of the mouse immune system, hence the name monoclonal, and can specifically target pathogens, tumor cells and other harmful agents. They can also be produced in large amounts for clinical use.
There are four types of monoclonal antibodies:
- Murine: entirely derived from a murine source. These mouse mAb are seen as foreign substances by the human immune system and thus provoke an immune response. This can have serious clinical side effects, and can also inactivate the mAb in the patient, rendering it therapeutically useless.
- Chimeric: the antigen-binding variable regions are of murine origin whereas the constant regions are human. These will also cause an immune response.
- Humanized: the mouse variable regions have been altered to make them look more like human antibodies and the constant regions are human. These mAb are clinically less problematic, but may eventually cause an immune response if injected repeatedly into patients.
- Human: entirely derived from a human source; they are very minimally immunogenic.
There are several different technologies available for antibody discovery. However, the most successful ones at fighting human diseases are those in which the mAb have been “humanized” or are fully-human. In the simplest terms, the more human a monoclonal antibody is, the better chance it has at successfully fighting human diseases.
Trianni Mouse Antibodies Are a Match for Humans
The Trianni Mouse™ is the only transgenic antibody discovery platform ever developed that contains the full-human antibody variable gene diversity in a single organism.
In The Trianni Mouse, the variable region gene segments are chimeric, but the variable domains of antibodies made by the mouse are entirely human. The constant region genes, which encode the parts of the antibody that interact with the rest of the mouse immune system, are mouse and thus optimized for function in the mouse. Once promising lead monoclonal antibodies are isolated, their human variable region genes can be easily isolated and grafted onto human constant region genes. The result is a fully human monoclonal antibody, ready for testing.
To learn more about the science behind The Trianni Mouse, please visit our Technology page.