A humanized antibody is an antibody from a non-human species that has been modified to increase its similarity to antibodies produced naturally in humans. This modification process involves retaining only the antigen-binding sites (complementarity-determining regions, CDRs) from the original non-human (often murine) antibody, while the rest of the antibody structure (the framework regions) is replaced with the corresponding human sequences. The goal is to reduce the immunogenicity of the antibody when used in humans, minimizing immune responses such as rejection or allergic reactions that could reduce the therapeutic efficacy of the antibody.

 Distinction from “Chimeric Antibody”

While both chimeric and humanized antibodies are genetically engineered to reduce immunogenicity and improve clinical efficacy in humans compared to fully murine antibodies, they differ in their composition and the extent of modification:

– Chimeric Antibodies: These antibodies are produced by combining the variable domains of a murine antibody (which are responsible for antigen binding) with the constant domains of a human antibody. Chimeric antibodies are thus part human and part mouse, with approximately 70% of the antibody being human. This modification significantly reduces their immunogenicity compared to fully murine antibodies but still can trigger immune responses because of the murine antigen-binding regions.

– Humanized Antibodies: In contrast to chimeric antibodies, humanized antibodies are designed to be even more similar to human antibodies. Only the CDRs of the murine antibody are grafted onto a human antibody framework. As a result, humanized antibodies consist of a greater proportion of human sequences (over 90%), further reducing the likelihood of immune responses when administered to patients.

 Application of Humanized Antibodies

Humanized antibodies have broad applications in the treatment of various diseases, especially in oncology, autoimmune diseases, and infectious diseases. Their reduced immunogenicity compared to murine and chimeric antibodies makes them particularly valuable for chronic treatments where long-term administration is required. Some notable applications include:

– Oncology: Humanized antibodies such as trastuzumab (Herceptin) target HER2 in breast cancer, improving outcomes for patients with HER2-positive breast cancer. Another example is alemtuzumab, which targets CD52 in lymphocytes and is used in the treatment of chronic lymphocytic leukemia.

– Autoimmune Diseases: Humanized antibodies like daclizumab, which targets the IL-2 receptor on activated T cells, have been used in the treatment of multiple sclerosis, reducing the frequency of relapses.

– Infectious Diseases: Palivizumab, a humanized antibody targeting the RSV virus, is used to prevent RSV infection in high-risk infants, demonstrating the utility of humanized antibodies beyond cancer and autoimmune diseases.

– Other Therapeutic Areas: The development of humanized antibodies continues to expand into other therapeutic areas, including cardiovascular diseases, transplant rejection, and allergic diseases, showcasing their versatility and potential in modern medicine.

In summary, humanized antibodies represent a significant advancement in antibody engineering, offering reduced immunogenicity and improved therapeutic profiles. Their development has led to significant improvements in the treatment of a wide range of diseases, with ongoing research likely to expand their applications further.