CD20 mimicry by a mAb rituximab-specific linear peptide: a potential tool for active immunotherapy of autoimmune diseases.
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.
Perosa
Federico
F
Department of Internal Medicine and Clinical Oncology (DIMO), University of Bari Medical School, Piazza Giulio Cesare 11, 70124 Bari, Italy.
Favoino
Elvira
E
Caragnano
Maria Antonietta
MA
Dammacco
Franco
F
D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D058846:Antibodies, Monoclonal, Murine-Derived; D000917:Antibody Formation; D018951:Antigens, CD20 / Q000276:immunology*; D001327:Autoimmune Diseases / Q000276:immunology / Q000628:therapy*; D000939:Epitopes; D005260:Female; D016233:Immunotherapy, Active; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D019151:Peptide Library; D000069283:Rituximab
D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D018951:Antigens, CD20; D000939:Epitopes; D019151:Peptide Library; D000069283:Rituximab