Antibody, humanization

Clark M (2000) Antibody humanization a case of the Emperor s new clothes Immunol Today 21(8) 397-402... 

Figure 13.9 Production of chimaeric (a) and humanized (b) antibodies (via recombinant DNA technology). Chimaeric antibodies consist of murine monoclonal VH and VL domains grafted onto the Fc region of a human antibody. Humanized antibody consists of murine CDR regions grafted into a human antibody...

DXM metabolism in rat brain microsomes is inhibited by quinidine and anti-CYP2D6 antibody human brain required exogenous reductase (Voirol et al., 2000). 

CD52 monoclonal antibody, humanized [SY] CAMPATH-1 [TR former reg. to Welcome Foundation]... 

Baca M, Presta LG, O Connor S J, Wells JA. 1997. Antibody humanization using monovalent phage display. J Biol Chem. 272 10678-10684. 

Figure 3. Immunohistochemical detection methods with therapeutic antibodies for analysis of human tissues. Therapeutic antibodies such as human-mouse chimeric antibody, humanized antibody, and completely human antibody are used as the primary antibody in these methods. A A method with hapten-labeled therapeutic antibody. B A method with non-labeled therapeutic antibody using a reagent that blocks endogenous human Igs.

Immune libraries and evolutionary selection strategies intersect in the area of antibody humanization. Recently, we have extended the repertoire of methods available for the generation of therapeutic human antibodies by developing phage display strategies for the selection and humanization of antibodies from immune animals other than mice. Our aim here was to modify protein sequence, in some cases in a very radical way, and yet retain the function of the parental antibody. In the following discussion, we will focus on these novel approaches. 

Although until recently antibody humanization was based on arduous rational design strategies that require computer modeling and itera-... 

Fig. 2. Selection strategy for antibody humanization that combines CDR grafting with framework fine-tuning. Nonhuman sequences are shown in gray, human sequences are white. The six CDRs of the nonhuman Fab are grafted into a human framework that contains a set of diversified residues. These residues are diversified to allow the selection of either the human or the original nonhuman residue. Reprinted with permission from Rader and Barbas (2000).

As described for antibody humanization, phage display strategies for selecting new antibodies can also be utilized to evolve existing antibodies. 

Types of Biopharmaceuticals Survey data on preclinical safety assessment programs were analyzed for 34 biopharmaceuticals cases. The numbers of antibodies, human proteins, and human protein analogues either in the development or marketed as of 2001 in Japan were 13,12, and 6, respectively. The remainder were bioconjugates, DNA-derived vaccines, and human T cell epitopes. Thus antibodies and human proteins are the two major biopharmaceuticals. 

Purification of Antibodies Humanized antibodies (hAB-1 and hAB-2) were purified by the technique of Protein-A chromatography, followed by Phenyl Sepharose and Ion-exchange chromatographies. The murine antibody (pMAB) was purified by Protein-A chromatography. 

Synonyms Campath-IH DNA-derived Humanized Monoclonal Antibody Humanized IgG I Anti-CD52 Monoclonal Antibody Trade names Campath (Berlex) MabCampath (Schering) Indications B-cell chronic lymphcyotic leukemia, non-Hodgkin s lymphoma... 

Chlorogen Plastid accumulation of vaccines, proinsulin, antibodies, human serum albumin 111-114... 

Monsanto/ Agracetus Monoclonal antibodies, single chain antibodies, Human growth hormone (plastid), collagen 170-177... 

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