Antibodies in diagnosis and therapy. The magic bullet--nearing the century mark.
A truly successful magic bullet therapy for cancer requires the production of agents which can easily reach, accurately recognize and permanently nullify every cancer cell in the body. Moreover, these precise functions must be achieved without adversely affecting normal vital tissues. This demanding approach is examined from the standpoint of animal model systems which satisfy these criteria to various extents. The salient features which contribute to success in these models are presented to provide a basis for evaluating the performance of currently available agents, and to assist in the design of new, more highly perfected 'bullets'. Pertinent issues regarding the therapeutic impact of cellular receptors, internalization pathways, mechanisms of toxin action, kinetics of cell killing, solid tumor penetration, pharmacokinetics and relative potency on target versus non-target cells are all considered. Current strategies using advanced biotechnical approaches to construct more effective targeted agents are addressed in this context.
Raso
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Boston Biomedical Research Institute, Department of Fine Structure Research, MA 02114.
D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D002470:Cell Survival / Q000187:drug effects; D004167:Diphtheria Toxin / Q000494:pharmacology; D006801:Humans; D000922:Immunotoxins / Q000096:biosynthesis / Q000494:pharmacology*; D009374:Neoplasms, Experimental / Q000276:immunology / Q000628:therapy*
D000911:Antibodies, Monoclonal; D004167:Diphtheria Toxin; D000922:Immunotoxins