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Blood, 1 February 2006, Vol. 107, No. 3, pp. 1070-1077. Prepublished online as a Blood First Edition Paper on October 13, 2005; DOI 10.1182/blood-2005-04-1769. This Article Full Text (PDF) All Versions of this Article: 2005-04-1769v1 107/3/1070    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Perosa, F. Articles by Dammacco, F. Search for Related Content PubMed PubMed Citation Articles by Perosa, F. Articles by Dammacco, F. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted May 2, 2005 Accepted September 28, 2005 Generation of biologically active linear and cyclic peptides has revealed a unique fine specificity of rituximab and its possible cross-reactivity with acid sphingomyelinase-like phosphodiesterase 3B precursor Federico Perosa*, Elvira Favoino, Maria A Caragnano, and Franco Dammacco Department of Internal Medicine and Clinical Oncology (DIMO), University of Bari Medical School, Bari, Italy * Corresponding author; email: f.perosa{at}dimo.uniba.it. Heterogeneity of the effector functions displayed by Rituximab and other anti-CD20 mAbs apparently recognizing the same CD20-epitope suggests that additional mechanisms, probably related to mAb fine specificity, are responsible for B cell depletion. To improve our understanding of Rituximab's function, its fine specificity was investigated by means of phage display peptide library (PDPL) expressing 7-mer cyclic (c7c) or 7-/12-mer linear peptides. Rituximab-specific c7c PDPL-derived clone insert sequences expressed the motif A(S)NPS, overlapping the human CD20 170ANPS173. P172 was the most critical for Rituximab-binding, since its replacement with S172 (of mouse CD20) abolished the reactivity. The WPXWLE-motif expressed by the linear PDPL-derived clone insert sequences could only be aligned to the reverse-oriented 161WPXWLE156 of acid sphingomyelinase-like phosphodiesterase-3b precursor (ASMLPD), though linear peptides bearing WPXWLE competed with cyclic ones for Rituximab-paratope binding. Anti-CD20 mAb 1F5 only displayed a reactivity profile similar to that of Rituximab, which also reacted with ASMLPD-derived peptides. Peptides induced antibodies with specificity and effector functions similar to those of Rituximab. Our results show a unique fine specificity of Rituximab, define the molecular basis for the lack of Rituximab reactivity with mCD20 and the potential of targeting CD20 in an active immunotherapy setting. A possible Rituximab interaction with ASMLPD is suggested. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: D. M. Goldenberg, E. A. Rossi, R. Stein, T. M. Cardillo, M. S. Czuczman, F. J. Hernandez-Ilizaliturri, H. J. Hansen, and C.-H. Chang Properties and structure-function relationships of veltuzumab (hA20), a humanized anti-CD20 monoclonal antibody Blood, January 29, 2009; 113(5): 1062 - 1070. [Abstract] [Full Text] [PDF] F. Perosa, E. Favoino, C. Vicenti, A. Guarnera, V. Racanelli, V. De Pinto, and F. Dammacco Two Structurally Different Rituximab-Specific CD20 Mimotope Peptides Reveal That Rituximab Recognizes Two Different CD20-Associated Epitopes J. Immunol., January 1, 2009; 182(1): 416 - 423. [Abstract] [Full Text] [PDF] S. Wagner, C. Krepler, D. Allwardt, J. Latzka, S. Strommer, O. Scheiner, H. Pehamberger, U. Wiedermann, C. Hafner, and H. Breiteneder Reduction of Human Melanoma Tumor Growth in Severe Combined Immunodeficient Mice by Passive Transfer of Antibodies Induced by a High Molecular Weight Melanoma-Associated Antigen Mimotope Vaccine Clin. Cancer Res., December 15, 2008; 14(24): 8178 - 8183. [Abstract] [Full Text] [PDF] B. Li, S. Shi, W. Qian, L. Zhao, D. Zhang, S. Hou, L. Zheng, J. Dai, J. Zhao, H. Wang, et al. Development of Novel Tetravalent Anti-CD20 Antibodies with Potent Antitumor Activity Cancer Res., April 1, 2008; 68(7): 2400 - 2408. [Abstract] [Full Text] [PDF] F. Perosa, E. Favoino, C. Vicenti, F. Merchionne, and F. Dammacco Identification of an Antigenic and Immunogenic Motif Expressed by Two 7-Mer Rituximab-Specific Cyclic Peptide Mimotopes: Implication for Peptide-Based Active Immunotherapy J. Immunol., December 1, 2007; 179(11): 7967 - 7974. [Abstract] [Full Text] [PDF] J. Du, H. Wang, C. Zhong, B. Peng, M. Zhang, B. Li, S. Huo, Y. Guo, and J. Ding Structural Basis for Recognition of CD20 by Therapeutic Antibody Rituximab J. Biol. Chem., May 18, 2007; 282(20): 15073 - 15080. [Abstract] [Full Text] [PDF] M. Binder, F.-N. Vogtle, S. Michelfelder, F. Muller, G. Illerhaus, S. Sundararajan, R. Mertelsmann, and M. Trepel Identification of Their Epitope Reveals the Structural Basis for the Mechanism of Action of the Immunosuppressive Antibodies Basiliximab and Daclizumab Cancer Res., April 15, 2007; 67(8): 3518 - 3523. [Abstract] [Full Text] [PDF] M. Binder, F. Otto, R. Mertelsmann, H. Veelken, and M. Trepel The epitope recognized by rituximab Blood, September 15, 2006; 108(6): 1975 - 1978. [Abstract] [Full Text] [PDF]

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