Creative Biolabs has established a universal antibody humanization platform to humanize monoclonal antibodies derived from a wide range of species. Non-human antibodies derived from canine, bovine, murine, rabbit, chicken, llama and camel can all be humanized. It is worth mentioning that we are certainly the only company in the field that has the expertise in monkey antibody humanization.
Non-human primate (NHP) antibody humanization is the process of modifying antibodies derived from non-human primates, such as monkeys, to make them more suitable for human therapeutics. NHPs have genetic similarities to humans, which allows NHP-derived antibodies to have better binding affinity for human targets than antibodies derived from other species. However, even fully non-human antibodies from NHPs can cause human immune responses. This immunogenicity can lead to serious adverse reactions, including antibody neutralization and hypersensitivity reactions.
To overcome these challenges, humanization modifies the structure of an antibody while retaining its ability to bind to the target antigen. The goal of humanization is to reduce the foreign, non-human elements in an antibody to make it more compatible with the human immune system. By replacing non-human sequences with human sequences, especially those in the constant regions of the antibody, the immune response triggered by the foreign antibody is minimized or eliminated. The complementarity determining regions (CDRs) responsible for antigen binding are retained to maintain the antibody's specificity and affinity. Through this process, NHP-derived antibodies can be transformed into therapeutic agents that closely resemble human antibodies, thereby optimizing their performance and minimizing potential side effects.
Fig. 1 Phylogenetic relationships among extant anthropoid primate lineages, including Old World monkeys, apes, and humans.
On the Universal Antibody Humanization platform, three-dimensional modeling of two vital monkey antibody frameworks is employed to identify the mutations that do not alter the parental antibody structure. After that, monkey antibodies are germline-humanized to frameworks very similar to human IgMs, which is supposed to be the best tolerated frameworks for therapeutic use while retaining the parental affinity. Using the same platform, Creative Biolabs is also professional in humanization of Bovine Ultralong CDR3s Antibodies and Humanized Single Domain Antibodies.
Rodent Antibody Humanization | NHP Antibody Humanization | |
Development Process |
Immunize rodents (mice or rats) with target antigen. Isolate antibodies and identify suitable candidates. Graft rodent antibody CDRs onto human frameworks. Apply optimization methods (affinity maturation, etc.). |
Immunize non-human primates with target antigen. Isolate antibodies with high affinity. Humanize by grafting NHP CDRs onto human antibody frameworks, optimizing for affinity and reducing immunogenicity. |
Applications |
Used for creating mAb in cancer immunotherapy, infectious diseases, and autoimmune disorders. Usually used for early stage research on new targets. |
Highly suitable for diseases where human or humanized antibodies are required. Ideal for therapeutic antibody development where high affinity and specificity are crucial. |
Advantages |
Faster and more cost-effective A broad range of libraries and techniques for antibody generation Suitable for developing a wide variety of antibodies |
High affinity and specificity Lower immunogenicity risk Closer to human antibodies in terms of structure and function |
Disadvantages |
Higher risk of immunogenicity when used in humans Reduced affinity in some cases post-humanization Require more rounds of optimization |
More complex and costly Ethical concerns and regulations Longer development timelines |
Examples of Use | Widely used in the development of research antibodies, diagnostic assays, and early-stage therapeutics. | Used in the development of high-affinity therapeutic antibodies, particularly for complex targets and diseases where human or humanized antibodies are critical. |
Non-human primates have significant advantages in producing high-quality therapeutic antibodies. By humanizing NHP-derived antibodies, it is possible to produce therapeutics that are highly specific, effective, and safe for humans. Creative Biolabs' advanced humanized platform, combined with sophisticated modeling and optimization techniques, is pushing the boundaries of what is possible in antibody development.
The primary purpose of humanizing NHP antibodies is to reduce their immunogenicity when used as therapeutic agents in humans. NHP antibodies, while similar to human antibodies, can still be recognized as foreign by the human immune system, leading to adverse immune responses. Humanization involves modifying the antibody's structure to make it more similar to human antibodies, thus reducing the likelihood of immune reactions. This process enhances the therapeutic potential of NHP antibodies by improving their safety profile and efficacy in human patients.
Humanization of NHP antibodies is typically achieved through a process called CDR grafting (Complementarity-Determining Region grafting). This technique involves transplanting the antigen-binding regions (CDRs) from the NHP antibody into a human antibody framework. The goal is to preserve the antigen-binding specificity and affinity of the original NHP antibody while replacing most of the molecule with human antibody sequences to minimize immunogenicity. Additional adjustments may also be made to improve the stability, expression, or further reduce the immunogenicity of the humanized antibody.
Yes, there are alternatives to humanizing NHP antibodies for therapeutic use, such as developing fully human antibodies through phage display or transgenic mice technologies. These methods involve creating libraries of human antibody genes that can be screened for molecules binding specifically to a target antigen, or utilizing mice genetically engineered to produce human antibodies in response to immunization. These approaches can produce antibodies that are inherently less immunogenic to humans than humanized NHP antibodies, potentially offering better safety profiles and reduced development times for therapeutic applications.
NHP antibodies are invaluable in preclinical medical research due to their close physiological and immunological similarities to humans. Before humanization, these antibodies can be used to study disease mechanisms, test therapeutic hypotheses, and validate the efficacy and safety of potential treatments in models that closely mimic human conditions. The use of NHP antibodies provides critical insights that can guide the development of humanized antibodies, ensuring that the therapeutic candidates are both effective and safe for clinical trials in humans.
Techniques such as molecular modeling and computational biology allow for precise mapping and modification of antibodies at the molecular level. These technologies help predict the effects of substituting human amino acids into the NHP antibody structure, thereby optimizing the design before physical production. Additionally, advanced screening technologies, like high-throughput sequencing and epitope mapping, provide detailed information on antibody-antigen interactions, facilitating more accurate humanization. These advancements enhance the efficiency and success rates of producing humanized antibodies that retain their desired biological activities.
Use the resources in our library to help you understand your options and make critical decisions for your study.
All listed services and products are For Research Use Only. Do Not use in any diagnostic or therapeutic applications.