Antibodies designed

Chester, K. Hawkins, R. (1995). Clinical issues in antibody design. Trends Biotechnol. 13, 294-300. 

The considerable list in Table 6.3 illustrates some of the companies that are currently preparing plant-based biopharmaceutical technologies for commercialization. Steps have been taken toward the development and subsequent commercialization of one of these products, currently in Phase 2 clinical trials and known as CaroRx (licensed to Planet Biotechnology Inc., Hayward, CA) a monoclonal antibody designed for treatment of tooth decay by S. mutans is described in the following text. 

Needless to say, intratumor penetration by antibodies remains a challenge. Even highly potent cytotoxic radionuclide-labeled antibodies designed to destroy cells neighboring those bound to the antibody do not completely eliminate abnormal cells in the core of a solid tumor. 

An understanding of Fey receptor gene polymorphism explains why some patients do not respond to monoclonal antibody, and it may broaden our understanding of monoclonal antibody activity and improve treatment outcomes in the future. Specific strategies include modulation of Fey receptor affinity or introduction of Fey receptor-reengineered monoclonal antibody designed to enhance binding to the Fey receptor. 

MDX-RA , an immunotoxin conjugated to an antibody designed to prevent secondary cataracts, phase III clinical trials, enrollment stopped. Medarex, Annandale, NJ. 

Catalytic antibodies generally do not approach the catalytic efficiency of enzymes, but medical and industrial uses for them are nevertheless emerging. For example, catalytic antibodies designed to degrade cocaine are being investigated as a potential aid in the treatment of cocaine addiction. 

Kufer, P., Mack, M., and Gruber, R., 1996. Construction and biological activity of a recombinant bi-specific single-chain antibody designed for therapy of minimal residual colorectal cancer. Cancer Immunol. Immunother. 45 193-197. 

Guidelines and methods for successful antibody design and production... 

Purification of T from retinal rod outer segments and of G0 from brain, provided yields of these proteins that were sufficient for partial amino acid sequence analysis of their proteolytic fragments. This analysis revealed that a subunits of G proteins, while quite distinct from each other in general terms, are nevertheless similar. A partial sequence of 21 amino acids was determined to be common in bovine rod cell T and bovine brain G0 [168], On the basis of this sequence, and other amino acid sequence analysis, four laboratories cloned cDNAs coding for transducin. The deduced amino acid structure of three of the cDNAs is the same [169-171] the fourth differed [172]. Peptide-directed antibodies designed to distinguish between the two cloned forms localized one to rod cells (T-r) and the other to cone cells (T-c) [173],... 

B cells are another type of white blood cell that creates antibodies designed specifically to attack a particular antigen. 

Schouten A, Roosien ), van Engelen FA, et al. The C-terminal KDEL sequence increases the expression level of a single-chain antibody designed to be targeted to both the cytosol and the secretory pathway in transgenic tobacco. Plant Mol. Biol., 1996 30(4) 781-793. 

With at least partial understanding of essential features of enzymatic catalysis has come the desire to improve, by the modification of existing enzymes through genetic or chemical means to alter their substrate specificity without loss of catalytic efficiency, the field of protein engineering. A unique feature in the antibody design is that the stereospecific catalysis can be sought for reactions not known to be enzyme catalyzed. 

Antibodies designed to catalyze the formation of a bond between two bound substrates suffer from the same problems of product inhibition as other enzyme mimics. Antibody 13D6.1, elicited through the phosphonate diester 161, catalyzed the transesteriflcation reaction (Figure 57) of ester 162 with alcohol 163 very efficiently with an effective molarity of s 10" -10 M but the formed product ester bound with a high affinity to the antibody ( diss = 18 uM) and thus inhibited turnover. " In favorable cases, the problem of product inhibition can be avoided by careful hapten design, as shown in the next example. 

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