In recent years, antibody therapy has become a new treatment modality for tumour patients, although the majority of responses are only partial and not long lasting. Based on evidence that effector-cell-mediated mechanisms significantly contribute to antibody efficacy in vivo, several approaches are currently persued to improve the interaction between Fc receptor-expressing effector cells and tumour target antigens. These approaches include application of Fc receptor-directed bispecific antibodies, which contain one specificity for a tumour-related antigen and another for a cytotoxic Fc receptor on immune effector cells. Thereby, bispecific antibodies selectively engage cytotoxic trigger molecules on killer cells, avoiding, for example, interaction with inhibitory Fc receptors. In vitro, chemically linked bispecific antibodies directed against the Fcγ receptors FcγRIII (CD16) and FcγRI (CD64), and the Fc α receptor FcαRI (CD89), were significantly more effective than conventional IgG antibodies. Recent animal studies confirmed the therapeutic potential of these constructs. However, results from clinical trials have been less promising so far and have revealed clear limitations of these molecules, such as short plasma half-lives compared with conventional antibodies. In this review, we briefly summarize the scientific background for bispecific antibodies, and describe the rationale for the generation of novel recombinant molecules. These constructs may allow us to more specifically tailor pharmacokinetic properties to the demands of clinical applications.
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August 2002
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Conference Article|
August 01 2002
Bispecific antibodies targeting cancer cells
M. Peipp;
M. Peipp
*Chair of Genetics, University Erlangen-Nürnberg, Staudtstrasse 5, D-91058, Erlangen, Germany
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T. Valerius
T. Valerius
1
†Division of Hematology/Oncology, Department of Medicine III, University Erlangen-Nürnberg, Krankenhausstrasse 12, D-91054 Erlangen, Germany
1To whom correspondence should be addressed (e-mail Thomas.Valerius@med3.imed.uni-erlangen.de)
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Publisher: Portland Press Ltd
Received:
March 11 2002
Online ISSN: 1470-8752
Print ISSN: 0300-5127
© 2002 Biochemical Society
2002
Biochem Soc Trans (2002) 30 (4): 507–511.
Article history
Received:
March 11 2002
Citation
M. Peipp, T. Valerius; Bispecific antibodies targeting cancer cells. Biochem Soc Trans 1 August 2002; 30 (4): 507–511. doi: https://doi.org/10.1042/bst0300507
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