Engineered antibodies take center stage

Huston, James S.; George, Andrew

doi:10.3233/hab-2001-103-405

Cited by 67 publications

(35 citation statements)

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“…This antibody therapy was initially targeted specifically for patients with advanced relapsed breast cancer that overexpresses HER-2 protein [262]. Since its launch in 1998, trastuzumab has become an important therapeutic option for patients with HER-2-positive breast cancer and is widely used for its approved indications in both the adjuvant and metastatic settings (Fig.…”

Section: Trastuzumab: Her-2 Testing and The Prediction Of Response Tomentioning

confidence: 99%

The HER-2 Receptor and Breast Cancer: Ten Years of Targeted Anti–HER-2 Therapy and Personalized Medicine

et al. 2009

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1. Contrast the current strengths and limitations of the three main slide-based techniques (IHC, FISH, and CISH) currently in clinical use for testing breast cancer tissues for HER-2 status.2. Compare the efficacy of trastuzumab-and lapatinib-based regimens in the adjuvant and metastatic settings as reported in published clinical trials and regulatory approval databases.3. Contrast the list of biomarkers that have been associated with clinical resistance to trastuzumab and lapatinib and describe their current level of validation.This article is available for continuing medical education credit at CME.TheOncologist.com. CME CME ABSTRACTThe human epidermal growth factor receptor (HER-2) oncogene encodes a transmembrane tyrosine kinase receptor that has evolved as a major classifier of invasive breast cancer and target of therapy for the disease. The validation of the general prognostic significance of HER-2 gene amplification and protein overexpression in the absence of anti-HER-2 targeted therapy is discussed in a study of 107 published studies involving 39,730 patients, which produced an overall HER-2-positive rate of 22.2% and a mean relative risk for overall survival (OS) of 2.74. The issue of HER-2 status in primary versus metastatic breast cancer is considered along with a section on the features of metastatic HER-2-positive disease. The major marketed slide-based HER-2 testing approaches, immunohistochemistry, fluorescence in situ hybridization, and chromogenic in situ

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Section: Trastuzumab: Her-2 Testing and The Prediction Of Response Tomentioning

confidence: 99%

The HER-2 Receptor and Breast Cancer: Ten Years of Targeted Anti–HER-2 Therapy and Personalized Medicine

et al. 2009

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“…8), was developed by Genentech (South San Francisco, CA) to specifically bind the extracellular portion of HER-2/neu. This antibody therapy was initially targeted specifically for patients with advanced relapsed breast cancer that overexpressed the HER-2/neu protein (165). Since its launch in 1998, trastuzumab has become an important therapeutic option for patients with HER-2/neu-positive breast cancer.…”

Section: Trastuzumab (Herceptin Tm )mentioning

confidence: 99%

Targeted Therapy in Breast Cancer

Ross

Fletcher

Bloom³

et al. 2004

Molecular & Cellular Proteomics

259

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The HER-2/neu oncogene, a member of the epidermal growth factor receptor or erb gene family, encodes a transmembrane tyrosine kinase receptor that has been linked to prognosis and response to therapy with the anti-HER-2-humanized monoclonal antibody, trastuzumab (Herceptin, Genentech, South San Francisco, CA) in patients with advanced metastatic breast cancer. HER-2/neu status has also been tested for its ability to predict the response of breast cancer to other therapies including hormonal therapies, topoisomerase inhibitors, and anthracyclines. This review includes an analysis of 80 published studies encompassing more than 25,000 patients designed to consider the relative advantages and disadvantages of the various methods of measuring HER-2/neu in clinical breast cancer specimens. Southern blotting, PCR amplification detection, and fluorescence in situ hybridization assays designed to detect HER-2/neu gene amplification are compared with HER-2/neu protein overexpression assays performed by immunohistochemical techniques applied to frozen and paraffin-embedded tissues and enzyme immunoassays performed on tumor cytosols. The significance of HER-2/neu overexpression in ductal carcinoma in situ and the HER-2/neu status in uncommon female breast conditions and male breast cancer are also considered. The role of HER-2/neu testing for the prediction of response to trastuzumab therapy in breast cancer is reviewed along with the current studies designed to test whether HER-2/neu status can predict the response to standard and newer hormonal therapies, cytotoxic chemotherapy, and radiation. The review will also evaluate the status of serum-based testing for circulating HER-

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“…Humanization and human antibody production are crucial procedures in passive immune therapy since murine antibodies fail to trigger a proper human immune response and instead elicit a human anti-mouse antibody response (19,20). However, one current challenge is that humanization often leads to loss of or changes in the effector activity of MAbs.…”

mentioning

confidence: 99%

A Novel Humanized Antibody Neutralizes H5N1 Influenza Virus via Two Different Mechanisms

Tan

Jia

et al. 2015

J Virol

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Highly pathogenic avian influenza virus subtype H5N1 continues to be a severe threat to public health, as well as the poultry industry, because of its high lethality and antigenic drift rate. Neutralizing monoclonal antibodies (MAbs) can serve as a useful tool for preventing, treating, and detecting H5N1. In the present study, humanized H5 antibody 8A8 was developed from a murine H5 MAb. Both the humanized and mouse MAbs presented positive activity in hemagglutination inhibition (HI), virus neutralization, and immunofluorescence assays against a wide range of H5N1 strains. Interestingly, both human and murine 8A8 antibodies were able to detect H5 in Western blot assays under reducing conditions. Further, by sequencing of escape mutants, the conformational epitope of 8A8 was found to be located within the receptor binding domain (RBD) of H5. The linear epitope of 8A8 was identified by Western blotting of overlapping fragments and substitution mutant forms of HA1. Reverse genetic H5N1 strains with individual mutations in either the conformational or the linear epitope were generated and characterized in a series of assays, including HI, postattachment, and cell-cell fusion inhibition assays. The results indicate that for 8A8, virus neutralization mediated by RBD blocking relies on the conformational epitope while binding to the linear epitope contributes to the neutralization by inhibiting membrane fusion. Taken together, the results of this study show that a novel humanized H5 MAb binds to two types of epitopes on HA, leading to virus neutralization via two mechanisms. IMPORTANCERecurrence of the highly pathogenic avian influenza virus subtype H5N1 in humans and poultry continues to be a serious public health concern. Preventive and therapeutic measures against influenza A viruses have received much interest in the context of global efforts to combat the current and future pandemics. Passive immune therapy is considered to be the most effective and economically prudent preventive strategy against influenza virus besides vaccination. It is important to develop a humanized neutralizing monoclonal antibody (MAb) against all of the clades of H5N1. For the first time, we report in this study that a novel humanized H5 MAb binds to two types of epitopes on HA, leading to virus neutralization via two mechanisms. These findings further deepen our understanding of influenza virus neutralization. R ecurrence of highly pathogenic avian influenza (HPAI) virus subtype H5N1 in humans and poultry continues to be a serious public health concern because of its unabated and widespread geographic circulation (1). Since their emergence in Asia over a decade ago, HPAI H5N1 viruses have spread to Ͼ60 countries on three continents and are endemic in poultry in Southeast Asia and Africa (2). They have caused disease in several mammals, including humans, often with lethal consequences. To date, H5N1 has resulted in 667 human cases worldwide, including 393 deaths (3). Although no sustained human-to-human transmission of the virus h...

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Engineered antibodies take center stage

Cited by 67 publications

References 0 publications

The HER-2 Receptor and Breast Cancer: Ten Years of Targeted Anti–HER-2 Therapy and Personalized Medicine

The HER-2 Receptor and Breast Cancer: Ten Years of Targeted Anti–HER-2 Therapy and Personalized Medicine

Targeted Therapy in Breast Cancer

A Novel Humanized Antibody Neutralizes H5N1 Influenza Virus via Two Different Mechanisms

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