The development of therapeutic antibodies has become a major focus of Genentech's research efforts in recent years. With the success of both Rituxan® and Herceptin®, the first therapeutic antibodies marketed in the United States for non-Hodgkin's lymphoma and breast cancer, respectively, Genentech now leads the biotech industry in the development of this important new drug category. In fact, nearly half of Genentech's current pipeline projects are evaluating new therapeutic antibodies or the further utility of Herceptin and Rituxan.
The Lymphatic System
Some therapeutic antibodies are capable of tracking down specific cells, such as cancer cells, and destroying them, without many of the debilitating toxic side effects of chemotherapy and radiation. But the promise of antibody therapy extends well beyond oncology. Genentech researchers are working to develop humanized therapeutic antibodies that target a variety of inflammatory and immunologic diseases, such as allergic asthma, inflammatory bowel disease, and psoriasis.
The first technology for making therapeutic antibodies was developed in 1975 by British scientists Milstein and Kohler, who were able to generate large quantities of uniform mouse antibodies designed to target specific proteins. However, these early mouse antibodies were of limited therapeutic value primarily due to the patients' allergic response to them. Genentech researchers have used recombinant DNA technology to create "humanized" antibodies — specially engineered versions of the human body's own antibodies — thereby lowering the risk of allergic response and making the drugs safer and more effective.
The proven therapeutic utility of humanized antibodies has encouraged researchers to find new methods for obtaining them, including ex vivo libraries and transgenic mice. Such mice generate antibodies with a human protein sequence instead of a mouse protein sequence. In addition, a variety of new techniques are being developed to further increase the efficacy and utility of these antibodies, such as linking toxins to the antibody. Genentech researchers are also studying other novel antibody forms that attack antigens aggressively or elicit an unusually strong response from the human immune system.