Monoclonal antibodies bifunctional

Wong SC, Chan JK, Lo ES, et al. The contribution of bifunctional SkipDewax pretreatment solution, rabbit monoclonal antibodies, and polymer detection systems in immunohistochemistry. Arch. Pathol. Lab. Med. 2007 131 1047-1055. 

Foglesong, P.D., Winkler, M.A., Price, J.O., Marshall, G.D., Reagh, S.H., Bush, D.A., Hixson, K.S., and West, W.H. (1989) Preparation and analysis of bifunctional immunoconjugates containing monoclonal antibodies OKT3 and BABR1. Cancer Immunol. Immunother. 30(3), 177-184. 

Subramanian, R., and Meares, C.F. (1991) Bifunctional chelating agents for radiometal-labeled monoclonal antibodies. In Cancer Imaging with Radiolabeled Antibodies (D.M. Coldenberg, ed.), pp. 183-199. Kluwer, Boston, MA. 

The purpose of a bifunctional chelator is to link a radiometal covalently to a targeting molecule such as a monoclonal antibody or a receptor-binding peptide. In the case of rhenium, the molecule therefore... 

The immunostaining procedure described below can be applied, in principle, to the quantification of any stabilized drug/protein - DNA adduct or complex where antibodies are available for that adduct or complex. The protocol provided below describes the detection and measurement of the adducts formed between the bifunctional alkylating drug melphalan and DNA, where monoclonal antibodies have been elicited against the adducts (3). 

Monoclonal antibodies represent a diverse group of therapeutic proteins typically presenting with complex pharmacokinetic properties [10]. For these compounds, more comprehensive, mechanism-based PBPK models have been described [96,97]. Baxter et al. developed and evaluated a bifunctional antibody PBPK model in mice and scaled the model to predict its pharmacokinetics in humans [96]. A membrane-... 

Westerberg D A, Carney P L, Rogers P E, et al. (1988). Synthesis of novel bifunctional chelators and their use in preparing monoclonal antibody conjugates for tumor targeting. J. Med. Chem. 32 236-243. 

Rogers B E, Anderson CJ, Connett J M,et al. (1996). Comparison of four bifunctional chelates for radiolabeling monoclonal antibodies with copper radioisotopes biodistribution and metabolism. Bioconjug. Chem. 7 511-522. 

Milenic D E, Roselli M, Mirzadeh S, et al. (2001). In vivo evaluation of bismuth-labeled monoclonal antibody comparing DTPA-derived bifunctional chelates. Cancer Biother. Radiopharm. 16 133-146. 

Pippin C J, Parker T A, McMurry T J, et al. (1992). Spectrophotometric method for the determination of a bifunctional DTPA ligand in DTPA-monoclonal antibody conjugates. Bioconjug. Chem. 3 342-345. 

As Cu has many interesting radionuclides for therapeutic as well as for diagnostic applications (O Tables 45. i and O 45.2), the development of ideal chelators for this metal is of interest. BFCs used for the coupling of Cu-radioisotopes to biomolecules are based on the 14-membered tetraazamacrocycle cyclam 14 (1,4,8,11-tetraazacyclotetradecane) O Fig. 45.17). Two bifunctional versions of cyclam-14, 4-[(l,4,8,ll-tetraazacyclotetradec-l-yl)methyl]-benzoic acid (= CPTA) and [6-(p-bromoacetamido)benzyl]-l,4,8,ll-tetraazacyclotetradecane-l,4,8,ll-tetraacetic acid (= BAT) (O Fig. 45.17), were coupled to monoclonal antibodies and somatostatin analogs (Smith-Jones et al. 1991 Anderson et al. 1995 Wilder et al. 1996). In addition to... 

Protein A/G-Ig complex can be stabilized with the bifunctional crosslinker dimethyl pimelimidate (24, 25). In this form the antibody on the column is oriented with the Fab arms free from the matrix and available for antigen binding Protocol 4). Complete kits for immobilization of antibody on Protein A or G are marketed by Pierce (IgG Orientation Kit), but any source of Protein A-or Protein G-agarose will do. The differences between Proteins A and G lie in the specificity for different immimoglobulin isotypes and species. Protein G in particular binds to rat IgG isotypes that Protein A does not. The majority of monoclonal antibodies made by conventional ceU fusion will be IgGs of mouse or rat origin, so Table 2 shows the relative affinities of these two proteins for different rodent IgG isotypes. 

Blend MJ, Stastny JJ, Swanson SM, Brechbiel MW. Labeling anti-HER2/neu monoclonal antibodies with lllln and 90Y using a bifunctional DTPA chelating agent. Cancer Biother Radiopharm 2003 3 355-363. 

Vosjan, M.J., Perk, L.R., Visser, G.W., Budde, M., Jurek, P., Kiefer, G.E., van Dongen, G.A., 2010. Conjugation and radiolabeling of monoclonal antibodies with zirconium-89 for PET imaging using the bifunctional chelate p-isothiocyanatobenzyl-desferrioxamine. Nat. Protoc. 5, 739—743. 

Fig. 1. Intracellular delivery of effector molecules using bispecific antibodies. A bifunctional carrier is constructed by linking a monoclonal anti-effector antibody to a monoclonal cell-targeting antibody. A noncovalent complex forms when the effector is added and binds to its specific antibody-combining sites. The targeting antibody directs this preformed complex to a distinct receptor site on the cell membrane. Alternatively, cells can be pretreated with the bispecific antibody, allowing the empty combining sites of the cell-bound reagent to be filled by subsequently added effector molecules. Surface-localized complexes quickly enter cells via a receptor-mediated endocytosis pathway. Escape of the effector from the cell vesicle system and passage into the cytosol is achieved but occurs slowly ( 24 h).

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