Little all-rounders hit the big time
Antibodies (or immunoglobulins) are essential building blocks of life and guarantors of human (and animal) health. They combat invading pathogens such as viruses, bacteria or toxins before these can do harm. Antibodies have now also become indispensable in medicine - both as highly specific active substances in latest generation drugs and as the basis of dependable diagnostic tests. At Roche, they are an important product group and a pillar of Personalised Healthcare.
Alongside Genentech in South San Francisco, Roche Penzberg in Bavaria is the site with the largest antibody know-how, and one of the leading biotechnology centers worldwide. The Penzberg Antibody Powerhouse encompasses the entire value chain from development to production, supplying Roche Pharma Research and Early Development (pRED) and Global Roche Group’s business areas with reliable, highly specific antibodies.
A major research focus in Penzberg is the development of investigational therapeutic antibodies for all the Roche Disease Biology Areas. Alongside classic preparation techniques such as the immunization of mice and rats, a method developed inhouse employing rabbits has been in use for some time. The ability to design new multi-active molecules for testing (by combining antibody fragments with one another or with other protein components) has also become possible through the development of alternative antibody formats. The bispecific CrossMAb formats are one example, created by combining parts from two different antibodies, thus allowing binding to two different antigens.
ttention is also focused on developing antibodies for the menu of immunoassays that run on Roche’s diagnostic platforms and for companion diagnostics. This requires special expertise in purifying antibodies, cleaving them into smaller-antigen binding units (fragmentation) and labeling them. “For our tests we need tremendously high affinity and specificity,” says Joachim Eberle, Head of Research at Roche Professional Diagnostics (RPD).
The development outlay is enormous. Starting with anywhere from 10,000 to 40,000 antibodies, the field is narrowed down to around 400 using suitable techniques. Further tests then yield around 10 candidates that are sent for final functional assessment.
From identifying the right antibody to devising a reliable method of production is yet another huge step which the development and production units in Penzberg handle with a combination of seasoned professionalism and creativity. While transferring and optimizing research production processes for industrial scale use and developing high-throughput fermentation and purification processes are governed by certain rules, they differ for each antibody, calling for great expertise in process development and process data management.
Well equipped for the future
Where are these little all-rounders headed? Ralf Schumacher, Head of Research at Pharma Research Early Development (pRED) Penzberg, has clear ideas about this: Modified antibodies are becoming increasingly important in new drug development: for example antibodies plus a toxin, antibodies with enhanced immunostimulation, and bispecific antibodies like the CrossMAb technology developed by Roche (pRED).
Bottom line: Penzberg has everything that’s needed to keep driving modern medicine forward. The Antibody Powerhouse is optimally equipped for the future.
Specificity is key
The immune system produces Y-shaped antibodies in response to antigens, i.e., substances that penetrate the body’s defenses and are identified as foreign by the immune system. When an antibody binds to its matching antigen, it triggers a reaction aimed at eliminating the intruder or rendering it innocuous. An antibody’s most important characteristic is its specificity, meaning that it always binds to a particular antigen. If the antigen is part of a disease-causing process, binding can interfere with the process and, ideally, abort it. If an antibody binds to a protein marker of a specific disease in a blood sample, the resulting antigenantibody complex can be detected, for example by its reaction to light, enabling the disease to be diagnosed.