Drug-antigen conjugate

When the resulting drug-antigen conjugate (D-Ag) is injected into the bloodstream of a rabbit, the immune system of the rabbit synthesizes antibodies with... 

Penicillins and cephalosporins bind irreversibly to serum albumin. It has been shown that drug-protein conjugates result from the aminolysis of the /3-lactam bond by the e-amino group of lysine residues in the protein (Fig. 5.1, Pathway e). The bound penicilloyl group appears to be the major antigenic determinant of penicillin allergy [145-148],... 

This antihypertensive drug was withdrawn from use after a number of cases of occulomucocutaneous syndrome (skin rashes, keratinization of the eye, and other tissues). Mechanism is unknown, but there is evidence for metabolism (microsomal enzyme mediated) to a reactive intermediate capable of reacting with protein and forming antigenic conjugates. Antipractolol antibodies are detected in patients. Syndrome is not reproducible in animals, but in hamsters, practolol accumulates in the eye. 

Radioactivity, however, is still a very sensitive means of measuring the presence or absence of a given material. Assay methodology has now come full circle, to the development of an ultrasensitive enzyme RIA. In this technique, an antigen is bound to a solid phase. Antibody will bind to the antigen, which could be a drug-protein conjugate, and the presence of bound antibody is detected by means of a second antibody coupled to alkaline phosphatase. So far this is the standard enzyme-linked immunosorbent assay (ELISA). However, if the substrate is tritium-labeled adenosine monophosphate, it is converted by the enzyme to tritium-labeled adenosine, which may be readily separated and measured. The detection limit for this assay for cholera toxin is approximately 600 molecules of the toxin (22). 

FIGURE 6.20 Formation of an antigenic drug-protein conjugate and subsequent stimulation of antibody production. The antibody so produced combines with the conjugate and inactivates it, in some cases by causing precipitation of the complex. 

Clinically, monoclonal antibodies are also proposed as drug delivery vehicles in certain tumors where specific tumor-associated antigens are expressed. In this context, investigators have found that by conjugating toxins such as the A chain polypeptide of the plant protein ricin or the bacterial toxin from Corynebacterium diphtheriae to monoclonal antibodies specific for certain tumor type, as few as one or two molecules of antibody-toxin conjugate can destroy a tumor cell in vitro. Some success has also been obtained in clinical trials with monoclonal antibody-toxin conjugates. 

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