subject: Humanization [print this page] In the field of medicinal research, therapeutic agents synthesized in non-human species need to be humanized for primary clinical trials, which will lead to large scale administration in humans. Without Humanization, all antibodies so synthesized are not similar to antibodies produced naturally in humans. Essentially, this potentially could result in rejection or destruction of these therapeutic agents by the human immune system immediately. Additionally, human immune system may also consider such protein sequences to be an external invasion, and react to such synthesized antibodies by developing antibodies to these, itself. Therefore, every, new iteration of lab research antibodies needs to be humanized for further testing and verification for stability, acceptability, and the resultant effects and side effects, and contraindications, if any.
Antibodies processed with "Humanization", are usually monoclonal antibodies synthesized for administration to humans (for example, antibodies developed as anti-cancer drugs). It may also be necessary for humanisation of a specific antibody, which involves generation in a non-human immune system (such as that in mice). The protein sequences of antibodies so developed are partially distinctive from homologous antibodies occurring naturally in humans. Hence, proving to be potentially immunogenic when administered to human patients. Humanization involves transmogrification of antibodies synthesized in non-human species in which the protein sequences have been modified for increasing their similarity to antibody variants produced naturally in humans. Antibody Humanization reduces the immunogenicity of monoclonal antibodies (mAbs) from xenogeneic sources (commonly rodent), and for improving their activation of the human immune system.
Humanized antibody is the critical step in reproducing the function of the original molecule. Today, the process of Humanization (also called Reshaping or CDR-grafting) is a well-established technique involving several mechanisms for creating antibodies synthesized in non-human species. The mechanics of producing an engineered mAb using the techniques of molecular biology is simple. Nonetheless, simple grafting of the rodent complementarity-determining regions (CDRs) into human frameworks does not, always, reconstitute the binding affinity and specificity of the original mAb.
From viable designs, researchers need to choose from the extents of the CDRs, the human frameworks to use, and the substitution of residues from the rodent mAb into the human framework regions (backmutations). A sequence/structural analysis or by analysis of a homology model of the variable regions' 3D structure determines the positions of such backmutations. Several other approaches to humanisation have been developed, which replace the surface rodent residues with the most common residues found in human mAbs ("resurfacing" or "veneering"), along with those which use differing definitions of the extents of the CDRs.
At Fusion Antibodies, murine monoclonal antibodies are effectively Humanized with the help of advanced strategies developed specifically to reduce the HAMA (Human Anti-Mouse Antibody) response in patients undergoing antibody therapy. Fusion Antibodies has delivered high quality results for hundreds of biotech companies, even on extremely challenging projects, successfully.
Pharmaceuticals, biotech companies, national and international research institutions have options to choose from 3 levels of Humanization services including:
Chimerisation
CDR grafting to a human germ line framework
CDR grafting to a human framework with somatic mutation (in-house know-how)
Fusion Antibodies offers quality, reliability, and quick turnaround. More than a 100 satisfied clients are happy to testify to the excellence of our ISO 9001 certified services.
Contact us now to request a quote for efficient antibody Humanization services.
Customized Humanization Services for Clinical Studies Worldwide
From the largest pharmaceutical to the smallest biotech company, we provide customized Humanization services to suit your requirements. That is why our UK-based CRO is the first choice of researchers around the world. Each client receives a comprehensive proposal for the Humanization and development of your antibodies put together by an experienced team of some of the best minds in the industry.
Fusion Antibodies has developed advanced technology for the rapid production of cell lines expressing full length recombinant antibodies and fully Humanized antibodies. Heres how we do it:
Murine Antibody VH and VL sequence
3 VH and VL variants designed
Recombined to give 9 possible Humanized Antibody variant vectors
Transfected in CHO
Cultured to 1mg level production for lead variant selection
Lead variant selected, Population undergoes MTX, Amplification steps
High production clones can be selected by ELISA
Cells banked and frozen and transferred to our cGMP partners
