Leveraging adcc to enhance anti-her2 therapy

Leveraging adcc to enhance anti-her2 therapy

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Access through your institution Buy or subscribe Outcomes of patients with HER2+ breast or gastroesophageal cancer are greatly improved with standard anti-HER2 antibody therapies, principally trastuzumab; however, resistance and disease relapse are common. The results of a first-in-human phase I study of a novel anti-HER2 antibody, margetuximab, indicate that enhanced immune-system engagement via antibody-dependent cell-mediated cytotoxicity (ADCC) might further improve outcomes. ADCC is triggered by the binding of antibodies to Fc receptors on immune effector cells. As lead author Yung-Jue Bang explains, “retrospective data have revealed unfavourable outcomes of trastuzumab treatment in patients expressing low-affinity alleles of the CD16A and CD32A Fc receptors, suggesting a role for ADCC in the antitumour activity of this agent; notably, most people are heterozygous or homozygous for these low-affinity isoforms.” He adds, “margetuximab has been Fc-modified to bind all allelic forms of CD16A and CD32A with increased affinity and, thus, to have greater potential to induce ADCC.” This is a preview of subscription content, access via your institution ACCESS OPTIONS Access through your institution Access Nature and 54 other Nature Portfolio journals Get Nature+, our best-value online-access subscription $29.99 / 30 days cancel any time Learn more Subscribe to this journal Receive 12 print issues and online access $209.00 per year only $17.42 per issue Learn more Buy this article * Purchase on SpringerLink * Instant access to full article PDF Buy now Prices may be subject to local taxes which are calculated during checkout ADDITIONAL ACCESS OPTIONS: * Log in * Learn about institutional subscriptions * Read our FAQs * Contact customer support REFERENCES * Bang, Y. J. _ et al_. First-in-human phase 1 study of margetuximab (MGAH22), an Fc-modified chimeric monoclonal antibody, in patients with HER2-positive advanced solid tumors. _Ann. Oncol._ http://dx.doi.org/10.1093/annonc/mdx002 (2017) Download references Authors * David Killock View author publications You can also search for this author inPubMed Google Scholar RIGHTS AND PERMISSIONS Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE Killock, D. Leveraging ADCC to enhance anti-HER2 therapy. _Nat Rev Clin Oncol_ 14, 200 (2017). https://doi.org/10.1038/nrclinonc.2017.19 Download citation * Published: 14 February 2017 * Issue Date: April 2017 * DOI: https://doi.org/10.1038/nrclinonc.2017.19 SHARE THIS ARTICLE Anyone you share the following link with will be able to read this content: Get shareable link Sorry, a shareable link is not currently available for this article. Copy to clipboard Provided by the Springer Nature SharedIt content-sharing initiative

Access through your institution Buy or subscribe Outcomes of patients with HER2+ breast or gastroesophageal cancer are greatly improved with standard anti-HER2 antibody therapies,


principally trastuzumab; however, resistance and disease relapse are common. The results of a first-in-human phase I study of a novel anti-HER2 antibody, margetuximab, indicate that enhanced


immune-system engagement via antibody-dependent cell-mediated cytotoxicity (ADCC) might further improve outcomes. ADCC is triggered by the binding of antibodies to Fc receptors on immune


effector cells. As lead author Yung-Jue Bang explains, “retrospective data have revealed unfavourable outcomes of trastuzumab treatment in patients expressing low-affinity alleles of the


CD16A and CD32A Fc receptors, suggesting a role for ADCC in the antitumour activity of this agent; notably, most people are heterozygous or homozygous for these low-affinity isoforms.” He


adds, “margetuximab has been Fc-modified to bind all allelic forms of CD16A and CD32A with increased affinity and, thus, to have greater potential to induce ADCC.” This is a preview of


subscription content, access via your institution ACCESS OPTIONS Access through your institution Access Nature and 54 other Nature Portfolio journals Get Nature+, our best-value


online-access subscription $29.99 / 30 days cancel any time Learn more Subscribe to this journal Receive 12 print issues and online access $209.00 per year only $17.42 per issue Learn more


Buy this article * Purchase on SpringerLink * Instant access to full article PDF Buy now Prices may be subject to local taxes which are calculated during checkout ADDITIONAL ACCESS OPTIONS:


* Log in * Learn about institutional subscriptions * Read our FAQs * Contact customer support REFERENCES * Bang, Y. J. _ et al_. First-in-human phase 1 study of margetuximab (MGAH22), an


Fc-modified chimeric monoclonal antibody, in patients with HER2-positive advanced solid tumors. _Ann. Oncol._ http://dx.doi.org/10.1093/annonc/mdx002 (2017) Download references Authors *


David Killock View author publications You can also search for this author inPubMed Google Scholar RIGHTS AND PERMISSIONS Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE


Killock, D. Leveraging ADCC to enhance anti-HER2 therapy. _Nat Rev Clin Oncol_ 14, 200 (2017). https://doi.org/10.1038/nrclinonc.2017.19 Download citation * Published: 14 February 2017 *


Issue Date: April 2017 * DOI: https://doi.org/10.1038/nrclinonc.2017.19 SHARE THIS ARTICLE Anyone you share the following link with will be able to read this content: Get shareable link


Sorry, a shareable link is not currently available for this article. Copy to clipboard Provided by the Springer Nature SharedIt content-sharing initiative