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Wednesday 01 June 2005

CD20 mimicry by a mAb rituximab-specific linear peptide: a potential tool for active immunotherapy of autoimmune diseases.

By: Perosa F, Favoino E, Caragnano MA, Dammacco F.

Ann N Y Acad Sci 2005 Jun;1051:672-83

An attractive, whether alternative or complementary, approach to passive immunotherapy (IT) with the anti-CD20 mAb rituximab for the treatment of autoimmune diseases is to stimulate the host to produce an anti-CD20 immune response by using peptides that mimic CD20 (mimotopes). The only mimotope reported to target CD20 antigen is a 43-mer polypeptide corresponding to the exposed domain of the molecule (from amino acid 142 to 184). Owing to its length, however, it failed to efficiently induce a CD20-specific response. A search has now been made for a smaller mimotope by biopanning a phage-display peptide library with rituximab. A total of 10 positive phage clones expressing six distinct sequences were isolated. Their alignment produced a motif that did not match any portion of the CD20 extracellular loop, whereas the motif bearing the 12-mer linear peptide Rp10-L specifically reacted with rituximab and inhibited its binding to CD20. Furthermore, in BALB/c mice Rp10-L-induced antibodies that reacted with the CD20(+) B lymphoid cell line Raji but not with the C20(-) T lymphoid cell line CEM. This peptide is currently being investigated to determine the effectiveness of CD20-based active IT for the treatment of autoimmune diseases.

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