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.
Theoretically, the best approach to obtain high affinity human antibodies is by constructing and screening of immunized human antibody libraries. However, we cannot immunize humans with all antigens of interest due to ethical reasons. As an alternative solution, monkeys (non human primates, NHPs) are regarded as one of the best substitutes with the germline sequences closest to human; humanization of monkey (NHP) antibodies opens a novel and highly efficient approach to produce quality therapeutic antibodies for human use.
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.
Other optional Human or Humanized Antibody Services:
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.
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