Monoclonal Antibodies mAbs

Currently, 17 mAbs have been approved in the United States (US) for therapeutic use in organ transplant, percutaneous coronary intervention, prophylaxis of respiratory syncytial virus, RA, Crohn s disease, asthma, chronic lymphocytic leukemia (CLL), acute myeloid leukemia, non-Hodgkin s lymphoma, breast cancer, and colorectal cancer. All approved mAbs are of the IgG class 13 human IgG1 one igG4, and two murine IgG2a. Thirteen are intact mAbs, three are conjugated, and one is a Fab fragment (Tables 12.2 to 12.4). 

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Davio et al. (43) report efforts to obtain monoclonal antibodies (mAbs) to STX. Because STX is a small molecule of approximately 300 daltons, well below the size necessary for immunogenicity, a carrier molecule must be conjugated to the hapten (STX). This technique must minimize alterations of the antigenic form. For the anti-STX antibodies tested to date, the ratios of immunoassay response factor to pharmacological potency for various STX derivatives differ substantially, the immunoassay being virtually unresponsive to some of the common natural derivatives (44). 

Watanabe et al. developed an enzyme-linked immunosorbent assay (ELISA) for the detection of inabenfide, a plant growth regulator, in rice. Specific monoclonal antibody (MAB) is used for this method. The effects of rice matrices on the sensitivity of ELISA can be reduced by adding 0.1% Tween 20. Good reproducibility and accuracy of the proposed ELISA were obtained for rice samples and the recovery was 92% at a fortification level of 5-500 xgkg . ... 

In the dialyzed batch start-up phase and the subsequent continuous operation a substantial increase in viable cell density and monoclonal antibody (MAb) titer was observed compared to a conventional suspension culture. The raw data, profiles of the viable cell density, viability and monoclonal antibody titer during the batch start-up and the continuous operation with a dialysis flow rate of 5 L/d are shown in Figures 17.6 and 17.7. The raw data are also available in tabular form in the corresponding input file for the FORTRAN program on data smoothing for short cut methods provided with the enclosed CD. 

Rabies virus protein Monoclonal antibody (mAb S057) Rabies virus neutralization N. tabacum cv Xanthi 35 S MSP +KDEL + 3 pg/g FLW (0.07% TSP) 33... 

Species differences must be considered when choosing a model and, in particular, species-specific immunological differences between the human and the test animal. For example, in humans, an anti-CD4 monoclonal antibody (MAb) will bind to CD4 expressed on monocytes, with subsequent fixing of complement and destruction of antigen-presenting cells. However, since CD4 molecules are not expressed on murine monocytes, these effects would not be evident in a murine model. 

Monoclonal antibody, mAb Describes an antibody derived from a single clone of cells or a clonally obtained cell line. Its common use denotes an antibody secreted by a hybridoma cell line. Monoclonal antibodies are used very widely in the study of antigens, and as diagnostics. 

Fig. 6.13. Schematic representation of a selective delivery obtained by antibody-directed en-zyme-prodrug therapy (ADEPT). An exogenous enzyme is coupled to a monoclonal antibody (mAb) targeted for tumor cells. In a second step, a prodrug is administered, which, as a selective substrate of the exogenous enzyme, will be selectively activated at the tumor site.

The most commonly used format for quantitation assays is the sandwich assay format. Typically, a monoclonal antibody (MAb) is used to capture the product. It is then detected by another antibody, usually enzyme-labeled. A reference standard is used from which to compare the response of an unknown test sample. There is a relative increase in measured response (optical density) with increasing analyte concentration. Figure 11.2 is an example of a typical ELISA standard curve. 

The next development was the production of monoclonal antibodies (MAbs) in the mid-1970s. This uses hybridoma technology, which involves the fusion of antibody-producing B cells to immortal myeloma cells. Figure 4.4 shows the preparation of MAbs using hybridoma techniques. A more detailed discussion of biopharmaceuticals production is presented in Section 10.5. 

Difficulties in detecting nucleolin on the cell surface could be explained by its very low concentration in this compartment (Hovanessian et al, 2000). Moreover, this cell surface expressed nucleolin protein has a different isoelectric point and it is recognized by only one monoclonal antibody (mAb D3) in its native conformation (Hovanessian et al, 2000). This probably reflects specific post-translational modifications undergone by nucleolin on the cell surface. Consistent with this hypothesis, extracellular nucleolin is a substrate of ecto-protein kinases including casein kinase II (Dumler et al, 1999 Jordan et al., 1994). Interestingly, indirect evidence suggests... 

Monoclonal antibodies (MAb) against tumour-associated antigens or growth factors using their intrinsic activity or used as carriers to target cytotoxic drugs, radionuclides and toxins (Section 8.5.1). 

Fig. 10 Formation of complexes between human rhinovirus HRV2 and neutralizing monoclonal antibody mAb 8F5 analyzed by CE. A fixed concentration of F1RV2 (15 nM) was incubated with an increasing concentration (indicated in the figure) of mAb 8F5 prior to the CE analysis at room temperature. O-phthalic acid was used as internal standard (IS). (Reprinted with permission from Ref. 34. Copyright 2000 American Chemical Society.)...

Mammalian cells are commonly employed for the production of therapeutic and diagnostic proteins, since they are able to correctly synthetize the large and complex structures that the human body requires as medicine [1]. Nowadays, they are employed for the large-scale production of recombinant therapeutic proteins, monoclonal antibodies (MAbs) and viruses used in the preparation of vaccines (e.g. against rabies, hepathytis B, polio, etc) [2]. An overview of some licensed/approved products derived from mammalian cell culture is given in Table 1. 

CEA-scan (Arcitumomab, murine monoclonal antibody (Mab) fragment (Fab), directed against human carcinoembryonic antigen, CEA)... 

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