title: Anti-tumor activity of a B-cell receptor-targeted peptide in a novel disseminated lymphoma xenograft model.
abstract: Receptor-targeted therapies have become standard in the treatment of various lymphomas. In view of its unparalleled specificity for the malignant B-cell clone, the B-cell receptor (BCR) on B cell lymphoma cells is a potential therapeutic target. We have used two BCR epitope mimicking peptides binding to the Burkitt's lymphoma cell lines CA46 and SUP-B8. We proved their functionality by demonstrating calcium flux and BCR-mediated endocytosis upon peptide receptor binding. Toxicity experiments in vitro via cross-linking of the BCR with tetramerized epitope mimics lead to apoptosis in both cell lines but was far more effective in SUP-B8 cells. We established a SUP-B8-based disseminated Burkitt's lymphoma model in NOD/SCID mice. Treatment of tumor-bearing mice with tetramerized epitope mimics had significant anti-tumor effects in vivo. We conclude that peptide-mediated, BCR-targeted therapy is a promising approach which may be explored and further developed for application in highly aggressive lymphoma.
authors.affiliation: Department of Hematology and Oncology, University of Freiburg Medical Center, Freiburg, Germany.
authors.forename: Claudia
authors.initials: C
authors.lastname: Wehr
authors.forename: Fabian
authors.initials: F
authors.lastname: Müller
authors.forename: Julia
authors.initials: J
authors.lastname: Schüler
authors.forename: Tina
authors.initials: T
authors.lastname: Tomann
authors.forename: Claudia
authors.initials: C
authors.lastname: Nitschke
authors.forename: Henning
authors.initials: H
authors.lastname: Seismann
authors.forename: Edzard
authors.initials: E
authors.lastname: Spillner
authors.forename: Kerstin
authors.initials: K
authors.lastname: Klingner
authors.forename: Tanja
authors.initials: T
authors.lastname: Schneider-Merck
authors.forename: Mascha
authors.initials: M
authors.lastname: Binder
authors.forename: Heinz-Herbert
authors.initials: HH
authors.lastname: Fiebig
authors.forename: Roland
authors.initials: R
authors.lastname: Mertelsmann
authors.forename: Martin
authors.initials: M
authors.lastname: Trepel
mesh_terms: D000818:Animals; D017209:Apoptosis; D002051:Burkitt Lymphoma / Q000188:drug therapy* / Q000473:pathology; D002118:Calcium / Q000378:metabolism; D045744:Cell Line, Tumor; D004705:Endocytosis; D018985:Epitopes, B-Lymphocyte / Q000276:immunology* / Q000378:metabolism; D005260:Female; D006801:Humans; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D018716:Molecular Mimicry; D058990:Molecular Targeted Therapy; D010455:Peptides / Q000276:immunology / Q000378:metabolism / Q000627:therapeutic use*; D011947:Receptors, Antigen, B-Cell / Q000378:metabolism*; D023041:Xenograft Model Antitumor Assays
chemical_list: D018985:Epitopes, B-Lymphocyte; D010455:Peptides; D011947:Receptors, Antigen, B-Cell; D002118:Calcium