An “Ab mouse,” or antibody mouse, is a genetically engineered laboratory mouse designed to produce human or human-like antibodies. These specialized mice represent a significant advancement in biological and medical research. They serve as living factories for generating antibodies that are highly compatible with the human immune system, which is immensely valuable for developing new therapies and understanding disease mechanisms.
The Need for Engineered Antibody Mice
Historically, the development of therapeutic antibodies faced a significant hurdle: the human immune system’s rejection of non-human antibodies. When traditional mouse-derived antibodies, known as murine antibodies, were introduced into human patients, the human immune system often recognized them as foreign substances. This recognition triggered an immune response, leading to the production of human anti-mouse antibodies (HAMA).
The HAMA response could range from mild allergic reactions, such as a rash, to severe and life-threatening conditions like kidney failure. This immune reaction also reduced the effectiveness of the treatment and could prevent future treatments with mouse antibodies from working. Consequently, a new approach was needed to create antibodies that would be effective in humans without eliciting such adverse immune responses.
Creating an Antibody Mouse
The creation of an antibody mouse involves sophisticated genetic engineering techniques. Scientists replace or modify the mouse’s own antibody-producing genes with human antibody-producing genes.
These engineered mice are designed so that their B cells produce fully human antibodies instead of mouse antibodies. When these mice are immunized with a specific antigen, their immune system generates a diverse repertoire of human antibodies that can bind to that target. This process allows for the natural diversification and selection of high-affinity human antibodies within a living system, mimicking the human immune response.
Applications in Science and Medicine
Antibody mice have revolutionized the development of therapeutic monoclonal antibodies, which are now used to treat a wide array of diseases. These mice are instrumental in creating antibodies for cancer, autoimmune disorders like rheumatoid arthritis and Crohn’s disease, and infectious diseases. For instance, fully human anti-epidermal growth factor receptor (EGFR) antibodies, developed using these models, have shown promise in inhibiting human cancer growth.
Beyond therapeutics, antibody mice contribute to vaccine development by providing a platform to test immune responses and generate antibodies against various pathogens. They are also used to understand human immunology, allowing researchers to study how the human immune system responds to different stimuli in a controlled environment. The ability of these mice to produce high-affinity, fully human antibodies has significantly accelerated the discovery and clinical translation of new antibody-based drugs.