Chimeric antibodies (CHM antibodies) are engineered molecules that combine genetic material from different species, typically human and murine (mouse), to enhance therapeutic efficacy and reduce immunogenicity. Developed through recombinant DNA technology, these antibodies merge the antigen-binding regions (variable regions) of a mouse monoclonal antibody with the constant regions of a human antibody. This design aims to retain the specificity and affinity of murine antibodies while minimizing adverse immune reactions often triggered by fully foreign proteins.
The concept emerged in the 1980s as scientists sought to overcome limitations of early murine-derived monoclonal antibodies, which were effective in targeting antigens but frequently caused human anti-mouse antibody (HAMA) responses. CHM antibodies became a pivotal innovation in immunotherapy, particularly for cancer and autoimmune diseases. For example, drugs like rituximab (anti-CD20) and infliximab (anti-TNF-α) utilize this chimeric structure to achieve targeted action with improved tolerability.
CHM antibodies laid the groundwork for subsequent generations of engineered antibodies, including humanized and fully human antibodies. Their development marked a milestone in biopharmaceuticals, enabling safer, long-term treatments and expanding the scope of precision medicine. Today, they remain widely used in clinical settings, underscoring their enduring impact on therapeutic antibody design.