Recombinant humanised anti-HER2/neu antibody (Herceptin®) induces cellular death of glioblastomas

Glioblastoma multiforme (GBM) remains the most devastating primary tumour in neuro-oncology. Targeting of the human epithelial receptor type 2 (HER2)-neu receptor by specific antibodies is a recent well-established therapy for breast tumours. Human epithelial receptor type 2/neu is a transmembrane tyrosine/kinase receptor that appears to be important for the regulation of cancer growth. Human epithelial receptor type 2/neu is not expressed in the adult central nervous system, but its expression increases with the degree of astrocytoma anaplasia. The specificity of HER2/neu for tumoral astrocytomas leads us to study in vitro treatment of GBM with anti-HER2/neu antibody. We used human GBM cell lines expressing HER2/neu (A172 express HER2/neu more than U251MG) or not (U87MG) and monoclonal humanised antibody against HER2/neu (Herceptin®). Human epithelial receptor type 2/neu expression was measured by immunohistochemistry and flow cytometry. Direct antibody effect, complement-dependent cytotoxicity and antibody-dependent cellular cytotoxicity were evaluated by different cytometric assays. We have shown, for the first time, the ability of anti-HER2/neu antibodies to induce apoptosis and cellular-dependent cytotoxicity of HER2/neu-expressing GBM cell lines. The results decreased from A172 to U251 and were negative for U87MG, in accordance with the decreasing density of HER2/neu receptors

HER2/neu: an increasingly important therapeutic target. Part 2: Distribution of HER2/neu overexpression and gene amplification by organ, tumor site and histology

No biological molecule in the field of oncology has been more extensively or more successfully targeted for therapeutic intent than the product of the c-erbB2 gene, HER2/neu. This is the second of a comprehensive three-part review of the foundation for and therapeutic targeting of HER2/neu. The distribution of HER2/neu overexpression and/or gene amplification by individual tumor sites and histologies will be comprehensively surveyed and described. This provides a bridge between the primarily basic science focused Part I, and the survey of clinical applications to follow in Part III. In combination, this comprehensive survey will identify opportunities and promising areas for future evaluation of HER2/neu-targeted therapies, highlighting the importance of HER2/neu as an increasingly important therapeutic target