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Status of Bispecific Monoclonal Antibodies for Cancer Therapy

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Summary

Native monoclonal antibodies (mAbs) have met with only limited success as therapeutic tools in the experimental treatment of human cancers. Therefore, alternative approaches for the therapeutic exploitation of the unique potential of mAbs to specifically target a tumour cell have been sought. One promising approach is bispecific mAbs, which have the capacity to bind to 2 different antigens and bring them into close proximity. If one arm of a bispecific mAb is directed against a tumour-associated antigen and the other against a cytotoxic agent such as a radionuclide, cytotoxic drug or cytotoxic effector cell, specific antitumour toxicity can be generated at the tumour site which will eventually lead to a specific tumour cell kill.

Bispecific mAbs binding to a trigger molecule on cytotoxic effector cells, for example natural killer cells or T lymphocytes, are able both to target and to activate these cells specifically at the tumour site. T lymphocytes triggered by a combination of 2 appropriate bispecific mAbs, which bind to a tumour-associated antigen and to the CD3 or CD28 antigen, respectively, might be the most potent tools for efficient activation of resting T lymphocytes and direction of their cytolytic activity against tumour cells.

Phase I/II trials for the clinical evaluation of bispecific mAbs are under way. The preliminary results indicate that anticancer bispecific mAbs will meet the therapeutic expectations once attributed to native mAbs.

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  1. Medizinische Klinik I, University of Saarland, Oscar Orth Strasse, 66421, Homburg/Saar, Germany

    Christoph Renner &  Michael Pfreundschuh

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Renner, C., Pfreundschuh, M. Status of Bispecific Monoclonal Antibodies for Cancer Therapy. Clin Immunother 5, 30–39 (1996). https://doi.org/10.1007/BF03259313

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