Monoclonal antibodies trastuzumab

A higher than expected incidence of CHF is also observed in patients treated with DOX and other cytotoxics (e.g., the taxane paclitaxel) or new generation targeted agents (e.g., the humanized anti-ErbB-2/neu monoclonal antibody trastuzumab) [3]. The cardiotoxic synergism of DOX with taxanes or... 

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. 

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. ... 

An interaction of doxorubicin with the anti-HER2 receptor humanized monoclonal antibody, trastuzumab (Herceptin), has been reported. Most patients who received trastuzumab in early trials had been pretreated with anthracyclines. Despite this, preliminary information suggested that reduced systolic cardiac function was an adverse effect of trastuzumab (119). More recently, this problem has been further highlighted in a study of women with metastatic breast cancer (120). Patients who had not received prior anthracycline-containing adjuvant chemotherapy were at greater risk of cardiotoxicity when they received trastuzumab in combination with doxorubicin or cyclophosphamide (27 and 75% respectively), compared with only 11% of patients who received trastuzumab in combination with pachtaxel (120,121). The risk of cardiac events in patients treated with doxorubicin, cyclophosphamide, and trastuzumab increased markedly after a cumulative doxorubicin dose of 360 mg/m. This suggests synergistic cardiotoxicity with trastuzumab and doxorubicin. Trastuzumab is therefore currently licensed only for use in conjunction with pacli-taxel or docetaxel and not with conventional doxorubicin. 

Hercep tin-2 Treatment of The humanized monoclonal antibody, trastuzumab, [36,37]... 

Mume E, Orlova A, Malmstrom P-U, et al. (2005). Radiobromination of humanized anti-HER2 monoclonal antibody trastuzumab using N-succinimidyl 5-bromo-3-pyridinecarboxylate, a potential label for immunoPET. Nucl. Med. Biol. 32 613-622. 

The extracellular domain of the HER-2 neu molecule is the therapeutic target for the specific IgGlx humanized chimeric monoclonal antibody Trastuzumab (Herceptin ), approved 1998 and found to be effective in malignancies with HER-2 overexpression. An important aspect of this specific immunotherapy includes the efficiency against non-proliferating disseminated tumor cells (dormant cells), which are usually in the GO phase of the cell cycle, where conventional chemotherapy is less effective. The HER-2 neu molecule is also the target for specific tyrosine kinase inhibitors such as Tykerb (lapatinib ditosylate), which block the kinase-substrate interaction and the extracellular tyrosine kinase receptors on tumor cells. 

Persson, M., Sivaev, 1., Winberg, K. J. et al. 2007. In vitro evaluation of two polyhedral boron anion derivatives as linkers for attachment of radioiodine to the anti-HER2 monoclonal antibody trastuzumab. Cancer Biother. Radiopharm., 22, 585-96. 

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. 

Trastuzumab is a monoclonal antibody directed against the HER-2/neu receptor. HER-2/neu is a member of the erbB (or HER) growth factor receptor family and is expressed at low levels in the epithelial cells of normal breast tissue. The overexpression of HER-2/neu is associated with increased transmission... 

Trastuzumab (Herceptin) -humanized mouse monoclonal antibody directed against HER-2/new receptor -fevers, chills, nausea, vomiting, headache during administration -cardiotoxicity (the FDA has not approved concurrent use with doxorubicin)... 

Trastuzumab, a monoclonal antibody that binds to HER2, produces response rates of 15% to 20% when used as a single agent and increases response rates, time to progression, and OS when combined with chemotherapy. It has been studied in doublet (taxane-trastuzumab vinorelbine-trastuzumab) and triplet (trastuzumab-taxane-platinum) combinations but the optimum regimen is unknown. 

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). 

Examples of antibodies in the market include trastuzumab (anti-HER2 monoclonal antibody), rituximab, natalizumab (x4-integiin antibody), abciximab, infiximab (targets TNF-a in Crohn s disease and rheumatoid arthritis), alemtuzumab, adalimumab (TNF-a antibody for the treatment of rheumatoid arthritis) and efalizumab (anti-CDlla monoclonal antibody for the treatment of psoriasis)Rituximab is a mouse/human chimeric anti-CD20 monoclonal antibody used for the treatment of various l)unphoid malignancies. As CE)20 antigen is found on the surface of... 

Immunomodulators affect the functioning of the immune system. Immune functions may be promoted as well as suppressed by these agents. In this section interferon alpha, BCG, immunocyanin and aldesleukine and the monoclonal antibodies, alem-tuzumab, bevacizumab, cetuximab, trastuzumab, rit-uximab and ibritumomab tiuxetan will be briefly discussed. 

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

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