The advent of monoclonal antibodies offers abundant potential benefits to diagnosis and therapy of many conditions. However, with widespread use come greater concerns regarding possible side effects and complications.

Antibodies, including monoclonals, react with antigens which may be represented on tissues other than those to which they were raised. Although histochemical surveys of tissues may be performed, these may not necessarily be predictive of in vivo cross-reactivities. This consideration mandates carefully performed preclinical toxicological studies prior to use in humans.

For murine monoclonal antibodies, the type most commonly available, issues related to potential immunogenicity are of paramount concern. Very little substantive information has accrued regarding the prevalence of these antibodies in the general population, the mechanism by which these antibodies are elicited, or the predictive value of assays for their detection. This knowledge is crucial for the development of strategies for blunting or controlling the human anti-mouse antibody response.

Contaminants in manufactured monoclonals also pose inherent danger to recipients. Among those commonly encountered are microbes, DNA, and manufacturing reagents (e.g., sera, column components, and tissue culture additives). Strict adherence to proper manufacturing technique usually will minimize these concerns. However, in the absence of well-defined cause/effect relationships between toxicity (theoretical or real) and agent, complacency that a given product is safe is ill-advised.

The Food and Drug Administration has disseminated a compilation of concerns and suggestions for addressing them in the document “Points to consider in the manufacture and testing of monoclonal antibody products for human use.” The precepts outlined in that document and a close working relationship between manufacturers of monoclonal products and scientifically astute regulators together represent an effective approach to minimizing the risks of monoclonal therapy in diverse patient populations.

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Presented at the “Second Conference on Radioimmunodetection and Radioimmunotherapy of Cancer,” September 8–10, 1988, Princeton, NJ.

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