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Targeting ADCC: A different approach to HER2 breast cancer in the immunotherapy era

The clinical outcome of patients with human epidermal growth factor receptor 2 (HER2) amplified breast carcinoma (BC) has improved with the development of anti-HER2 targeted therapies. However, patients can experience disease recurrence after curative intent and disease progression in the metastatic...

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Autores principales: Mandó, Pablo, Rivero, Sergio G., Rizzo, Manglio M., Pinkasz, Marina, Levy, Estrella M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8399304/
https://www.ncbi.nlm.nih.gov/pubmed/34454323
http://dx.doi.org/10.1016/j.breast.2021.08.007
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author Mandó, Pablo
Rivero, Sergio G.
Rizzo, Manglio M.
Pinkasz, Marina
Levy, Estrella M.
author_facet Mandó, Pablo
Rivero, Sergio G.
Rizzo, Manglio M.
Pinkasz, Marina
Levy, Estrella M.
author_sort Mandó, Pablo
collection PubMed
description The clinical outcome of patients with human epidermal growth factor receptor 2 (HER2) amplified breast carcinoma (BC) has improved with the development of anti-HER2 targeted therapies. However, patients can experience disease recurrence after curative intent and disease progression in the metastatic setting. In the current era of evolving immunotherapy agents, the understanding of the immune response against HER2 tumor cells developed by anti-HER2 antibodies (Abs) is rapidly evolving. Trastuzumab therapy promotes Natural Killer (NK) cell activation in patients with BC overexpressing HER2, indicating that the efficacy of short-term trastuzumab monotherapy, albeit direct inhibition of HER, could also be related with antibody-dependent cell-mediated cytotoxicity (ADCC). Currently, dual HER2 blockade using trastuzumab and pertuzumab is the standard of care in early and advanced disease as this combination could confer an additive effect in ADCC. In patients with disease relapse or progression, ADCC may be hampered by several factors such as FcγRIIIa polymorphism and an immunosuppressive environment, among others. Hence, new drug development strategies are being investigated aiming to boost the ADCC response triggered by anti-HER2 therapy. In this review, we summarize these strategies and the rationale, through mAbs engineering and combinatorial strategies, focusing on clinical results and ongoing trials.
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spelling pubmed-83993042021-09-02 Targeting ADCC: A different approach to HER2 breast cancer in the immunotherapy era Mandó, Pablo Rivero, Sergio G. Rizzo, Manglio M. Pinkasz, Marina Levy, Estrella M. Breast Review The clinical outcome of patients with human epidermal growth factor receptor 2 (HER2) amplified breast carcinoma (BC) has improved with the development of anti-HER2 targeted therapies. However, patients can experience disease recurrence after curative intent and disease progression in the metastatic setting. In the current era of evolving immunotherapy agents, the understanding of the immune response against HER2 tumor cells developed by anti-HER2 antibodies (Abs) is rapidly evolving. Trastuzumab therapy promotes Natural Killer (NK) cell activation in patients with BC overexpressing HER2, indicating that the efficacy of short-term trastuzumab monotherapy, albeit direct inhibition of HER, could also be related with antibody-dependent cell-mediated cytotoxicity (ADCC). Currently, dual HER2 blockade using trastuzumab and pertuzumab is the standard of care in early and advanced disease as this combination could confer an additive effect in ADCC. In patients with disease relapse or progression, ADCC may be hampered by several factors such as FcγRIIIa polymorphism and an immunosuppressive environment, among others. Hence, new drug development strategies are being investigated aiming to boost the ADCC response triggered by anti-HER2 therapy. In this review, we summarize these strategies and the rationale, through mAbs engineering and combinatorial strategies, focusing on clinical results and ongoing trials. Elsevier 2021-08-19 /pmc/articles/PMC8399304/ /pubmed/34454323 http://dx.doi.org/10.1016/j.breast.2021.08.007 Text en © 2021 Published by Elsevier Ltd. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Review
Mandó, Pablo
Rivero, Sergio G.
Rizzo, Manglio M.
Pinkasz, Marina
Levy, Estrella M.
Targeting ADCC: A different approach to HER2 breast cancer in the immunotherapy era
title Targeting ADCC: A different approach to HER2 breast cancer in the immunotherapy era
title_full Targeting ADCC: A different approach to HER2 breast cancer in the immunotherapy era
title_fullStr Targeting ADCC: A different approach to HER2 breast cancer in the immunotherapy era
title_full_unstemmed Targeting ADCC: A different approach to HER2 breast cancer in the immunotherapy era
title_short Targeting ADCC: A different approach to HER2 breast cancer in the immunotherapy era
title_sort targeting adcc: a different approach to her2 breast cancer in the immunotherapy era
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8399304/
https://www.ncbi.nlm.nih.gov/pubmed/34454323
http://dx.doi.org/10.1016/j.breast.2021.08.007
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