Anti-tumor activity of a B-cell receptor-targeted peptide in a novel disseminated lymphoma xenograft model

作者：Wehr Claudia; Mueller Fabian; Schueler Julia; Tomann Tina; Nitschke Claudia; Seismann Henning; Spillner Edzard; Klingner Kerstin; Schneider Merck Tanja; Binder Mascha; Fiebig Heinz Herbert; Mertelsmann Roland; Trepel Martin^*

来源：International Journal of Cancer, 2012, 131(2): E10-E20.

DOI：10.1002/ijc.26464

• phage display
• B-cell receptor
• Burkitt%26apos
• s lymphoma
• xenograft model
• epitope mimic

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%26apos;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%26apos;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.

• 出版日期2012-7-15