Anti-tumor activity of a B-cell receptor-targeted peptide in a novel disseminated lymphoma xenograft model.
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Anti-tumor activity of a B-cell receptor-targeted peptide in a novel disseminated lymphoma xenograft model. / Wehr, Claudia; Müller, Fabian; Schüler, Julia; Tomann, Tina; Nitschke, Claudia; Seismann, Henning; Spillner, Edzard; Klingner, Kerstin; Schneider-Merck, Tanja; Binder, Mascha; Fiebig, Heinz-Herbert; Mertelsmann, Roland; Trepel, Martin.
In: INT J CANCER, Vol. 131, No. 2, 2, 2012, p. 10-20.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Anti-tumor activity of a B-cell receptor-targeted peptide in a novel disseminated lymphoma xenograft model.
AU - Wehr, Claudia
AU - Müller, Fabian
AU - Schüler, Julia
AU - Tomann, Tina
AU - Nitschke, Claudia
AU - Seismann, Henning
AU - Spillner, Edzard
AU - Klingner, Kerstin
AU - Schneider-Merck, Tanja
AU - Binder, Mascha
AU - Fiebig, Heinz-Herbert
AU - Mertelsmann, Roland
AU - Trepel, Martin
PY - 2012
Y1 - 2012
N2 - 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.
AB - 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.
M3 - SCORING: Journal article
VL - 131
SP - 10
EP - 20
JO - INT J CANCER
JF - INT J CANCER
SN - 0020-7136
IS - 2
M1 - 2
ER -