A Huge Leap of the mAb Drug Against Tumor—Humanized Monkey Antibody
Posted: Nov 21, 2019
It's a common sense among the professionals working in the field of anti-tumor medicine that the antibody drugs outperform traditional ones in efficacy on a large scale, of which the humanized mAbs are a pillar rock in midstream.
Overview of antibody humanization
Original mAb drugs come from immunization in mice, like Muromonab-cd3, the first new monoclonal antibody drug approved by FDA in history, which have high immunogenicity and are liable to induce human body produce corresponding antibodies, and thus neutralized the drugs themselves. As a result, since the 1980s, scientists have been dedicated to cutting down immunogenicity in the mAbs by increasing the proportion of sequences from human body in the antibody sequence, which was the first attempt of humanization. Yet the humanized antibody whose host is rodent still can not achieve satisfactory efficacy as there are still alloplasmic sequences. As technology advances, methods in this stream have evolved too. Creative Biolabs, as a conscientious CRO in the field of antibody humanization, has worked out a way to humanize antibodies from monkey (non human primate, NHP), leading the whole industry.
The notion of adopting monkeys' antibody originates from their close relationship with human beings, and the unsatisfactory test results of rodent animals. In order to accelerate the research steps in the whole field, a humanization platform has been designed that accepts not simply rabbit, dog, chicken, but also monkey antibodies for humanization, on which two crucial NHP’s 3D antibody prototypes are built so as to detect mutations.
Major techniques adopted during the NHP antibody humanization process:
CDR Grafting & SDR Grafting—complementarity-determining region grafting combined with specificity-determining residue grafting to ensure lessening the immunogenicity of the resulting antibody as much as possible, even in the residues.
Chain Shuffling Strategy—based on construction and screening of two chimeric phage display libraries to orderly shift the light chain and heavy chain of antibody for further screening, which enables full humanization.
Humanized IgG Library Screening—a mammalian cell surface display approach allowing selecting humanized antibodies in a full-size IgG format, and support protein synthesis.
NHPs are involved in the study of more than 70 kinds of human infectious diseases, including pathogens like bacteria, viruses, fungi, parasites and prions; infectious diseases like global infectious diseases, children's infectious diseases, tropical infectious diseases, sexually transmitted diseases, new infectious diseases, zoonoses, potential bioterrorism, etc. Creative Biolabs’s NHP humanization solutions can solve most of the problems encountered by researchers and medicine manufactures that large-scale experiments on NHPs are costly and confined to high experimental standards, that systematic fundamental immunological information of NHPs’ gene, protein metabolites and signaling pathways are lacked. Furthermore, the application of NHP humanized antibodies in immunotherapy is hopeful to become more common to fix with the high risk of immune reaction stimulated by humanized rodent antibodies.
With years of dedicated exploration in humanization and monoclonal antibody researches, the scientists at Creative Biolabs are professional to provide highly specific and affinity improved human monoclonal antibodies, especially from NHPs. More details can be reached at https://www.creative-biolabs.com/.
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