MAb

In Sections V.A.1-V.A.3, we treated one particular group of t mabices as presented in Eq. (51), where g is an antisymmebic matrix with constant elements. The general theory demands that the mabix D as presented in Eq. (52) be diagonal and that as such it contains (-1-1) and (—1) values in its diagonal. In the three examples that were worked out, we found that for this particular class of T mabices the coiiesponding D mabix contains either (-1-1) or (—1) terms but never a mixture of the two types. In other words, the D mab ix can be represented in the following way ... 

MABS copolymers Macadam roads Macallum s PPS process MacArthur process... 

In 1975, the first successful production of MAbs was reported (44). By fusing normal antibody-producing cells with a B-ceU tumor (myeloma), hybridoma cell lines resulted which produced antibodies having a specificity to only one deterrninant on an antigen ie, all the antibodies produced from the cell line are identical. These studies resulted in a standard approach to MAb production. In this approach, the hybridoma cells are produced in large quantities in culture and screened to select specific clones producing the desired MAb using an appropriate assay. The selected clones are then expanded in culture (or in animals), the cells are collected, and the MAbs are extracted and purified. 

The singularity of MAbs and the ease of mass production appeared to be the answer to rapid development of highly specific immunoassays. Companies were formed to produce MAbs and incorporate them into assays. In fact, such assays have been developed and have proved very successful for infectious diseases, hormones, and other clinical analytes. 

Whereas MABs appear to be the choice for use in immunoassays, a majority of immunoassay developers and suppHers use polyclonal antibodies. 

The question of whether to use MAbs or PAbs in an assay is a matter of assay requirements (specificity and sensitivity) and economics and caimot be answered on technical merit alone. 

A review covers the preparation and properties of both MABS and MBS polymers (75). Literature is available on the grafting of methacrylates onto a wide variety of other substrates (76,77). Typical examples include the grafting of methyl methacrylate onto mbbers by a variety of methods chemical (78,79), photochemical (80), radiation (80,81), and mastication (82). Methyl methacrylate has been grafted onto such substrates as cellulose (83), poly(vinyl alcohol) (84), polyester fibers (85), polyethylene (86), poly(styrene) (87), poly(vinyl chloride) (88), and other alkyl methacrylates (89). 

Fig. 6. General reaction scheme for the preformed chelate approach where Bz = benzoyl and MAb = monoclonal antibody.

MBS = methyl methacrylate—butadiene—styrene and MABS = methacrylate-acrylonitrile—butadiene—styrene. 

Denusomab (anti-RANKL mAb) Growth factors (e.g. GH, IGFs, FGFs)... 

OPG has been shown to reduce bone turnover in postmenopausal women. More recently, Denusomab, an anti-RANKL mAb, has been tested for its ability to increase BMD and to reduce bone turnover. Results were promising and clinical phase III studies with fracture endpoints are presently under way. 

Intracellular single-chain mAbs are supposed to prevent membrane localization of the receptors. Antireceptor mAbs conjugated to radionucleides, or to prodrugs, are tested as well, and DNA vaccines may induce an active immune response against RTK overexpressing tumors. 

A number of chimerized, humanized, and one human mAb have now been approved for therapeutic use in humans in the treatment of autoimmunity, malignancy, infection and cardiovascular disease (Table 1). Some of the currently licensed mAb will be discussed here. A much larger number of mAb are currently being evaluated in Phase I, II and III trials. In general, chimeric, humanized and human mAb are very well tolerated with few side effects. Chimeric or humanized mAb still have the potential to evoke host immune response to the variable domains or CDRs of the antibody so-called HACA (human anti-chimeric antibody) or HAHA (human anti-human antibody) responses, although these responses are uncommon. Short-lived and occasionally severe infusion-related acute hypersensitivity reactions such as fever, skin itching, shivering, respiratory compromise and low blood pressure sometimes occur-. Such effects may... 

The chimeric human/murine (basiliximab and dacluzi-mab) or murine (inolimomab) monoclonal antibodies are specifically directed against a part (CD25) of the interleukin-2 (IL-2) receptor. Binding of one of these antibodies to CD25 thereby displaces physiological IL-2 and prevents proliferation of activated T-lymphocytes. 

Herceptin, (Trastuzu-mab) Monoclonal antibody against receptor EGFR2 ErbB-2/neu/ HER-2 Cancer Clinic... 

The potential of B lymphocyte depletion as an approach to therapy has been confirmed in RA patients seropositive for rheumatoid factor and/or anti-CCP antibodies using the anti-CD20 mAb, rituximab. 

Mehrishi JN, Szabo M, Bakacs T (2007) Some aspects of the recombinantly expressed humanised superagonist anti-CD28 mAb, TGN1412 trial catastrophe lessons to safeguard mAbs and vaccine trials. Vaccine 25 3517-3523... 

Trastuzumab (Herceptin ) Roche mAb HER-2 HER-2 overexpressing breast cancer in the adjuvant and metastatic settings... 

Bevacizumab (Avastin ) Roche mAb VEGFR Metastatic colorectal cancer... 

Cetuximab specifically binds the extracellular domain of EGFR. It has been approved in colorectal and head and neck cancer. However, unlike for trastuzu-mab, no clear correlation has been demonstrated between EGFR expression in cancer cell and efficacy of cetuximab. 

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