Abstract
Antibodies are traditionally viewed as targeting entities that are used to specifically recognize and target other molecules, antigens, or receptors. However, there are occasions in which cognate ligands are generated against the antibodies themselves. The number of useful applications that rely on the recognition and targeting of antibodies extends to various diseases, including cancer, inflammation, and autoimmune disorders. For example, anti-idiotypic antibodies have been generated to target surface immunoglobulins on neoplastic B-lymphocytes and plasma cells for the treatment of lymphomas and leukaemias (1,2). Such idiotypic determinants are tumor-specific, and have been exploited in a number of immunotherapeutic approaches, either in the form of vaccines (3–11) or as the target of anti-idiotypic antibodies (12–24). The latter, in particular, have been used successfully both in the unconjugated mono- and bi-specific forms (13,14,17), or as conjugates to other agents such as interleukin-2 (18–20), cytotoxic drugs (23), or radioisotopes (12,22). In addition to haematological malignancies, antibodies are also implicated in autoimmune disorders and transplant rejection, and they could become possible targets in the management of these conditions. On the other hand, antigenmimics, whether structural, functional or both, can be produced against a target antibody. Such mimics have been used in raising antibodies (25) and as anti-inflammatory and anti-tumor agents (26).In addition, RNA aptamers have recently been used as antigen mimics to elude patient autoantibodies from binding to acetylcholine receptors in the control of myasthenia gravis (27). Finally, molecules with binding specificity for antibodies could also be used in the generation of immunoaffinity matrices for the purification of antibodies. To fulfill the promise of antibody targeting, significant interest has emerged in the generation of peptide ligands against antibody targets using phage-display generated peptide libraries (28). However, the structural freedom of peptides and the resulting entropic cost upon target binding limit the use of peptide libraries in which high-affinity and specificity are required (29, 30). Moreover, amino acids are not interactive with each other in the way that nucleotides are, causing most small peptides to be unstructured in solution, whereas structurally stable proteins are large (31)
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Missailidis, S. (2004). Targeting of Antibodies Using Aptamers. In: Lo, B.K.C. (eds) Antibody Engineering. Methods in Molecular Biology™, vol 248. Humana Press. https://doi.org/10.1385/1-59259-666-5:547
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DOI: https://doi.org/10.1385/1-59259-666-5:547
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