Monoclonal antibodies in cancer treatment: where do we stand after 10 years?

Monoclonal antibodies (MoAbs) with specificity to tumour-associated antigens have become increasingly available during the past years. Presently, they are being applied in various in vitro diagnostic assays. They have contributed to the knowledge of cancer biology to a large extent. The understanding of cell surface characteristics and antigenic phenotype of tumours has in particular influenced the approach in the treatment of leukemias and lymphomas. From successful tumour localization in patients by gamma-emitting radio-labelled MoAbs it became clear, that these proteins offer a unique possibility to target therapeutic agents to tumour sites. The mere administration of MoAbs did not result in sufficient clinical benefit, but with proper precautions high doses of murine antibody were well tolerated. In order to use MoAbs as a carrier system, various toxins, cytostatic drugs, or radionuclides have been conjugated to these proteins. Thus far, specific problems were encountered not only associated with the immunoconjugate itself, but also to its fate in the patient. With regard to the substantial knowledge on the use of MoAbs in vivo obtained from animal tumour models, immunoscintigraphy in patients, and phase I serotherapy trials, we will undoubtedly determine the optimal conditions required for a conjugated anti-tumour agent to achieve enhanced cytotoxicity without increased side-effects. Preliminary results with high doses of 131I-labelled MoAbs in patients having tumour lesions expressing relevant antigens encourage further studies with immunoconjugates in cancer treatment. While much work needs to be done to further define the role of MoAbs as a new treatment modality in malignancies, this area of immunotherapy deserves great emphasis for the development of effective conjugates for future patients.