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128. Kongress der Deutschen Gesellschaft für Chirurgie

Deutsche Gesellschaft für Chirurgie

03.05. - 06.05.2011, München

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Oncolytic designer peptides as an therapy option to treat soft tissue sarcomas

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  • Jennifer Hauk - BG Universitätskliniken Bergmannsheil, Ruhr-Universität Bochum, Klinik für Plastische Chirurgie und Schwerbrandverletzung, Bochum
  • Frank Jacobsen - BG Universitätskliniken Bergmannsheil, Ruhr-Universität Bochum, Klinik für Plastische Chirurgie und Schwerbrandverletzung, Bochum
  • Cornelius Schubert - BG Universitätskliniken Bergmannsheil, Ruhr-Universität Bochum, Klinik für Plastische Chirurgie und Schwerbrandverletzung, Bochum
  • Stefan Langer - BG Universitätskliniken Bergmannsheil, Ruhr-Universität Bochum, Klinik für Plastische Chirurgie und Schwerbrandverletzung, Bochum
  • Ingo Stricker - BG Universitätskliniken Bergmannsheil, Ruhr-Universität Bochum, Institut für Pathologie, Bochum
  • Sammy Al-Benna - BG Universitätskliniken Bergmannsheil, Ruhr-Universität Bochum, Klinik für Plastische Chirurgie und Schwerbrandverletzung, Bochum
  • Yechiel Shai - Weizmann Institute of Science, Rehovot
  • Hans-Ulrich Steinau - BG Universitätskliniken Bergmannsheil, Ruhr-Universität Bochum, Klinik für Plastische Chirurgie und Schwerbrandverletzung, Bochum
  • Lars Steinstraesser - BG Universitätskliniken Bergmannsheil, Ruhr-Universität Bochum, Klinik für Plastische Chirurgie und Schwerbrandverletzung, Bochum

Deutsche Gesellschaft für Chirurgie. 128. Kongress der Deutschen Gesellschaft für Chirurgie. München, 03.-06.05.2011. Düsseldorf: German Medical Science GMS Publishing House; 2011. Doc11dgch627

doi: 10.3205/11dgch627, urn:nbn:de:0183-11dgch6275

Published: May 20, 2011

© 2011 Hauk et al.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by-nc-nd/3.0/deed.en). You are free: to Share – to copy, distribute and transmit the work, provided the original author and source are credited.

Outline

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Introduction: Soft tissue sarcoma (STS) is an anatomically and histologically heterogeneous neoplasia that shares a putative mesenchymal cell origin. The treatment with common chemotherapeutics is still unsatisfying because of association with poor response rates. Although evidence is accumulating for potent oncolytic activity of host defense peptides (HDPs), their potential therapeutic use is often limited by poor bioavailability and inactivation in serum. Therefore, we tested the designer host defense-like lytic D,L-amino acid peptide [D]-K3H3L9 on two STS cell lines in vitro and also in an athymic and syngeneic mouse model. In recent studies the peptide could show selectivity against prostate carcinoma cells and also an active state in serum.

Materials and methods: The human synovial sarcoma cell line SW982, the murine fibrosarcoma cell line BFS-1 and primary human fibroblasts as a control were exposed to [D]-K3H3L9, a 15mer D,L-amino acid designer HDP. Cell vitality in physiological and acidic conditions (MTT-assay), cell growth (BrdU) and DNA-fragmentation (TUNEL) were investigated. Membrane damage at different time points could be analyzed with LDH assay. An antibody against the tested peptide could give an inside in the mode of action. In vivo [D]-K3H3L9 was administered intratumorally in an athymic and syngeneic (immune competent) mouse model with SW982 and BFS-1 cells, respectively. After three weeks tumor sections were histologically analyzed.

Results: The peptide exerts rapid and high significant cytotoxicity and antiproliferating activity against the malignant cell lines, apparently via a membrane disrupting mode of action. The local intratumoral administration of [D]-K3H3L9 in the athymic and syngeneic mice models significantly inhibited tumor progression. The histological analyses of the tumor sections revealed a significant antiproliferative activity of the treatment group.

Conclusion: These findings demonstrate the in vitro and in vivo oncolytic activity of [D]-K3H3L9 in athymic and syngeneic mouse models.