Humanized mice antibody production full#

Diphtheria antitoxin, the antigen-specific IgG fraction isolated from the serum of diphtheria immunized horses, is still in use today. Prior to the development of mAb technologies, antisera from hyperimmunized animals were used to treat infectious diseases such as botulism and diphtheria. The use of antibodies as therapeutics has a long history. Understanding, controlling and engineering around potential immunogenicity is therefore of interest to the industry. A heightened awareness of these issues has developed as the field matures and the clinical consequences of immune responses to therapeutics have been reported and detailed. Immunogenic responses to antibody therapeutics can impact both safety and pharmacokinetic properties which can impact utility and efficacy of the drugs. However, the use of mAbs in clinical settings has been complicated by a number of technical challenges including the demonstration of immunogenic responses. Monoclonal antibodies (mAbs) represent effective therapeutic agents as they demonstrate significant specificity for their targets and confer effector functions such as receptor-ligand blockade, target cell cytotoxicity and receptor antagonism. Modifications to CDR regions can be designed that reduce the immunogenic potential while maintaining the bioactivity of the antibody molecule. A consequence of this result is modifications to reduce immunogenicity will be centered on the affinity-determining regions.

We propose that immunogenicity will always be present in some antibody molecules due to the nature of the antigen-specific combining sites.

Humanized mice antibody production full#

We were able to incorporate up to two amino acid modifications in a single epitope that reduced the immunogenic potential while retaining full biologic function. In spite of these differences, CD4 + T cell epitopes were found only in CDR-sequence containing regions. the antibodies studied represented a number of different VH and VL family members carrying unique CDR regions. to more fully understand the immunologic potential of humanized and human antibodies, we analyzed CD4 + helper T cell epitopes in a set of eight humanized antibodies. However, some humanized and even fully human sequence-derived antibody molecules still carry immunological risk.

Humanization, the replacement of mouse constant regions and V framework regions for human sequences, results in a significantly less immunogenic product. Humanization of murine monoclonal antibodies has vastly improved their in vivo tolerability. Monoclonal antibodies represent an attractive therapeutic tool as they are highly specific for their targets, convey effector functions and enjoy robust manufacturing procedures.