gms | German Medical Science

27. Deutscher Krebskongress

Deutsche Krebsgesellschaft e. V.

22. - 26.03.2006, Berlin

Chemotherapeutic agents enhance gene transfer with an adeno-associated virus-based vector into breast cancer cells

Meeting Abstract

  • corresponding author presenting/speaker Christian Kurzeder - Universitätsfrauenklinik, Ulm, Deutschland
  • Bernd Koppold - Universitätsfrauenklinik, Ulm
  • Hildegard Büning - Universität zu Köln, Medizinische Klinik I, Köln
  • Rolf Kreienberg - Universitätsfrauenklinik, Ulm
  • Helmut Deissler - Universitätsfrauenklinik, Ulm
  • Christian Kurzeder - Universitätsfrauenklinik, Ulm

27. Deutscher Krebskongress. Berlin, 22.-26.03.2006. Düsseldorf, Köln: German Medical Science; 2006. DocPO477

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Veröffentlicht: 20. März 2006

© 2006 Kurzeder et al.
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Supplementing conventional treatment with gene therapy as an unrelated approach to eradicate malignant cells might be beneficial to breast cancer patients. In addition to direct tumor suppression, transient expression of a therapeutic transgene can induce a persistent immune response to characteristics of the malignant phenotype. Recombinant adeno-associated viruses (rAAVs) are considered superior vectors to mediate gene transfer into tumor cells. They are able to infect a broad range of cell types and, derived from a helper virus-dependent and non-pathogenic parvovirus, they meet critical safety requirements. In this study, we evaluated the efficiency of transduction of breast cancer cells with rAAVs and potential effects of co-administration of cytotoxic agents and the anti-Her-2 antibody Herceptin used in adjuvant breast cancer therapy. In clear contrast to previous studies, infection of eight cell lines with an EGFP-encoding rAAV (50 infectious particles per cell) resulted in fractions of transgene-expressing cells up to 93 %. Transduction was completely neutralized by heparin, a known in vitro-inhibitor of AAV infection. Pre-incubation of MM 157, MM 231 and MCF7 cells (showing only moderate susceptibility to AAV transduction) with epirubicin or carbplatin substantially increased AAV-mediated transgene expression, which was not affected by Herceptin. Conclusion: The efficiency of rAAV-mediated gene transfer into breast cancer cells is significantly higher than previously reported and can be further enhanced by co-administration of chemotherapeutic agents. This provides a basis for for future therapeutic approaches including intratumoral gene transfer.