Humanized antibodies are antibodies in which the constant regions (i.e., the CH and CL regions) or the entire antibody are encoded by human antibody genes.

The application of antibody humanization is primarily focused on the development of therapeutic antibodies, particularly for the treatment of various diseases such as cancer, autoimmune diseases, and infectious diseases. Through the antibody humanization process, antibodies originally produced by non-human sources (such as mice) are modified into forms that are more compatible with the human immune system, thereby reducing patients’ immune responses to these antibodies. This makes these antibodies safer and more effective in clinical use. In addition, humanized antibodies play a significant role in the development of diagnostic and research tools, as they are capable of specifically recognizing human disease biomarkers. Antibody humanization technology is an integral part of modern drug development. It not only enhances the safety and efficacy of treatments but also opens new avenues for a deeper understanding of diseases. Ongoing research and technological innovation are key to driving progress in this field.

(1) Reducing immunogenicity: Non-human (e.g., mouse) antibodies may trigger immune reactions in humans, such as human anti-mouse antibody (HAMA) reactions. Through humanization, the non-human portions of the antibody are replaced with their human counterparts, thereby reducing the risk of immune reactions. (2) Maintaining Affinity and Specificity: Maintaining an antibody’s binding specificity and affinity during the humanization process is a challenge that requires the precise identification and retention of key amino acid residues. For example, the complementary determining regions (CDRs) are typically left unchanged because they bind directly to the antigen. (3) Enhancing Safety and Efficacy in Clinical Applications: Humanized antibodies are better suited for therapeutic use because their behavior in the human body more closely resembles that of naturally produced antibodies. (4) Advances in Technical Methods: Modern biotechnology, particularly the development of computational methods and machine learning tools, has made the humanization process more efficient and accurate. For example, computational tools such as Hu-mAb can suggest mutations to an input sequence to reduce its immunogenicity, which is faster and more effective than traditional trial-and-error experimental methods.