Department of Hematology and Oncology, University of Freiburg Medical Center, Freiburg, Germany.
Int J Cancer. 2012 Jul 15;131(2):E10-20. doi: 10.1002/ijc.26464. Epub 2011 Nov 19.
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.
受体靶向治疗已成为治疗各种淋巴瘤的标准方法。鉴于其对恶性 B 细胞克隆的无与伦比的特异性，B 细胞淋巴瘤细胞上的 B 细胞受体 (BCR) 是一个潜在的治疗靶点。我们使用了两种结合 Burkitt 淋巴瘤细胞系 CA46 和 SUP-B8 的 BCR 表位模拟肽。通过证明肽受体结合后钙通量和 BCR 介导的内吞作用，我们证明了它们的功能。通过交联 BCR 与四聚体表位模拟物进行的体外毒性实验导致两种细胞系发生凋亡，但在 SUP-B8 细胞中更为有效。我们在 NOD/SCID 小鼠中建立了基于 SUP-B8 的弥漫性 Burkitt 淋巴瘤模型。用四聚体表位模拟物治疗荷瘤小鼠在体内具有显著的抗肿瘤作用。我们得出结论，肽介导的 BCR 靶向治疗是一种很有前途的方法，可用于探索和进一步开发用于治疗高度侵袭性淋巴瘤。
