Trastuzumab, cancer monoclonal antibody

Recombinant humanized monoclonal antibodies have been used recently to target antigens that are preferentially located on cancer cells. Examples include trastuzumab and rituximab which are used to treat HER2 positive breast cancer and B-cell type lymphomas, respectively. Unwanted side effects include anaphylactic reactions. 

Umemura, S., Sekido, Y., Itoh, H., and Osamura, RY. 2002. Pathological evaluation of HER2 overexpression for the treatment of metastatic breast cancers by humanized anti-HER2 monoclonal antibody (trastuzumab). Acta Histochemica et Cytochemica, Kyoto 35(2), 77-81. 

Goldenberg, M.M., "Trastuzumab, a Recombinant DNA Derived Monoclonal Antibody, a Novel Agent for the Treatment of Metastatic Breast Cancer," Clin. Ther., 21, 309-318 (1999). 

Olver IN. Trastuzumab as the lead monoclonal antibody in advanced breast cancer choosing which patient and when. Future Oncol 2008 4(1) 125-31. 

While no biopharmaceutical is approved with the requirement of genotyping as a part of its therapeutic indication, a recently approved monoclonal antibody therapy against breast cancer, trastuzumab (Herceptin), is indicated only for those tumors measurably expressing the protein expressed by the gene erbB-2. Because the oncogene product of erbB-2 is elevated... 

Trastuzumab is a recombinant DNA-derived, humanized monoclonal antibody that binds to the extracellular domain of the human epidermal growth factor receptor HER-2/ . This antibody blocks the natural ligand from binding and down-regulates the receptor. Trastuzumab is approved for the treatment of metastatic breast cancer in patients whose tumors overexpress HER-2/ . As a single agent it induces remission in about 15-20% of patients in combination with chemotherapy, it increases response rate and duration as well as 1-year survival. Trastuzumab is under investigation for other tumors that express HER-2... 

First-line treatment of her metastatic breast cancer should therefore incorporate the monoclonal antibody trastuzumab (Herceptin). NICE (2002b) have issued a technology appraisal on the use of trastuzumab in metastatic breast cancer which states that trastuzumab be used in combination with paclitaxel for women with tumours with excessive human epidermal growth factor receptor 2 (HER2) at levels of 3+ who have not had chemotherapy for metastatic breast cancer and for whom anthracycline treatment is inappropriate. ... 

Trastuzumab exemplifies a growing number of monoclonal antibodies that have become available for antineoplastic therapy. These are directed against cell surface proteins that are strongly expressed by cancer cells. Trastuzumab binds to HER2, the recep-Luellmann, Color Atlas of Pharmacology All rights reserved. Usage subject to terms... 

Molina, M. A., Codony-Servat, J., Albanell, J., Rojo, F., Arribas, J., and Baselga, J. (2001). Trastuzumab (herceptin), a humanized anti-Her2 receptor monoclonal antibody, inhibits basal and activated Her2 ectodomain cleavage in breast cancer cells. Cancer Res. 61, 4744-4749. 

---