Selective death of human breast cancer cells by lytic immunoliposomes: Correlation with their HER2 expression level

Trastuzumab (Herceptin (TM)) targets the human epidermal growth factor receptor 2 (HER2), which is overexpressed in 20-30% of breast and ovarian cancers carrying a bad prognosis. Our purpose was to target HER2-overexpressing human breast cancer cells with pegylated immunoliposomes bearing trastuzumab and containing melittin, which has recently shown anticancer properties. Using a panel of human breast cancer cells with different HER2 expression levels, these immunoliposomes decreased cancer cells viability in a dose-response manner and in correlation to their level of HER2 expression. Specific binding of the immunoliposomes to SKBr3 breast cancer cells was shown by ImageStream-based analysis. The morphological changes observed in the treated cells suggested a cytolytic process. This preclinical approach may suppose an effective strategy for the treatment of HER2-overexpressing tumors, and can support the development of an early phases I-II clinical trial. Trastuzumab resistant breast cancer cells (JIMT-1), can also be targeted using this approach. (C) 2009 Elsevier Ireland Ltd. All rights reserved.