Leveraging ADCC to enhance anti-HER2 therapy

Killock, David

doi:10.1038/nrclinonc.2017.19

Research Highlight
Published: 14 February 2017

Targeted therapy

Leveraging ADCC to enhance anti-HER2 therapy

David Killock

Nature Reviews Clinical Oncology volume 14, page 200 (2017)Cite this article

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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.”

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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)

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