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Tumor-Directed Blockade of CD47 with Bispecific Antibodies Induces Adaptive Antitumor Immunity
CD47 serves as an anti-phagocytic receptor that is upregulated by cancer to promote immune escape. As such, CD47 is the focus of intense immuno-oncology drug development efforts. However, as CD47 is expressed ubiquitously, clinical development of conventional drugs, e.g., monoclonal antibodies, is c...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6698848/ https://www.ncbi.nlm.nih.gov/pubmed/31544856 http://dx.doi.org/10.3390/antib7010003 |
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author | Dheilly, Elie Majocchi, Stefano Moine, Valéry Didelot, Gérard Broyer, Lucile Calloud, Sébastien Malinge, Pauline Chatel, Laurence Ferlin, Walter G. Kosco-Vilbois, Marie H. Fischer, Nicolas Masternak, Krzysztof |
author_facet | Dheilly, Elie Majocchi, Stefano Moine, Valéry Didelot, Gérard Broyer, Lucile Calloud, Sébastien Malinge, Pauline Chatel, Laurence Ferlin, Walter G. Kosco-Vilbois, Marie H. Fischer, Nicolas Masternak, Krzysztof |
author_sort | Dheilly, Elie |
collection | PubMed |
description | CD47 serves as an anti-phagocytic receptor that is upregulated by cancer to promote immune escape. As such, CD47 is the focus of intense immuno-oncology drug development efforts. However, as CD47 is expressed ubiquitously, clinical development of conventional drugs, e.g., monoclonal antibodies, is confronted with patient safety issues and poor pharmacology due to the widespread CD47 “antigen sink”. A potential solution is tumor-directed blockade of CD47, which can be achieved with bispecific antibodies (biAbs). Using mouse CD47-blocking biAbs in a syngeneic tumor model allowed us to evaluate the efficacy of tumor-directed blockade of CD47 in the presence of the CD47 antigen sink and a functional adaptive immune system. We show here that CD47-targeting biAbs inhibited tumor growth in vivo, promoting durable antitumor responses and stimulating CD8(+) T cell activation in vitro. In vivo efficacy of the biAbs could be further enhanced when combined with chemotherapy or PD-1/PD-L1 immune checkpoint blockade. We also show that selectivity and pharmacological properties of the biAb are dependent on the affinity of the anti-CD47 arm. Taken together, our study validates the approach to use CD47-blocking biAbs either as a monotherapy or part of a multi-drug approach to enhance antitumor immunity. |
format | Online Article Text |
id | pubmed-6698848 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-66988482019-09-05 Tumor-Directed Blockade of CD47 with Bispecific Antibodies Induces Adaptive Antitumor Immunity Dheilly, Elie Majocchi, Stefano Moine, Valéry Didelot, Gérard Broyer, Lucile Calloud, Sébastien Malinge, Pauline Chatel, Laurence Ferlin, Walter G. Kosco-Vilbois, Marie H. Fischer, Nicolas Masternak, Krzysztof Antibodies (Basel) Article CD47 serves as an anti-phagocytic receptor that is upregulated by cancer to promote immune escape. As such, CD47 is the focus of intense immuno-oncology drug development efforts. However, as CD47 is expressed ubiquitously, clinical development of conventional drugs, e.g., monoclonal antibodies, is confronted with patient safety issues and poor pharmacology due to the widespread CD47 “antigen sink”. A potential solution is tumor-directed blockade of CD47, which can be achieved with bispecific antibodies (biAbs). Using mouse CD47-blocking biAbs in a syngeneic tumor model allowed us to evaluate the efficacy of tumor-directed blockade of CD47 in the presence of the CD47 antigen sink and a functional adaptive immune system. We show here that CD47-targeting biAbs inhibited tumor growth in vivo, promoting durable antitumor responses and stimulating CD8(+) T cell activation in vitro. In vivo efficacy of the biAbs could be further enhanced when combined with chemotherapy or PD-1/PD-L1 immune checkpoint blockade. We also show that selectivity and pharmacological properties of the biAb are dependent on the affinity of the anti-CD47 arm. Taken together, our study validates the approach to use CD47-blocking biAbs either as a monotherapy or part of a multi-drug approach to enhance antitumor immunity. MDPI 2018-01-03 /pmc/articles/PMC6698848/ /pubmed/31544856 http://dx.doi.org/10.3390/antib7010003 Text en © 2018 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Dheilly, Elie Majocchi, Stefano Moine, Valéry Didelot, Gérard Broyer, Lucile Calloud, Sébastien Malinge, Pauline Chatel, Laurence Ferlin, Walter G. Kosco-Vilbois, Marie H. Fischer, Nicolas Masternak, Krzysztof Tumor-Directed Blockade of CD47 with Bispecific Antibodies Induces Adaptive Antitumor Immunity |
title | Tumor-Directed Blockade of CD47 with Bispecific Antibodies Induces Adaptive Antitumor Immunity |
title_full | Tumor-Directed Blockade of CD47 with Bispecific Antibodies Induces Adaptive Antitumor Immunity |
title_fullStr | Tumor-Directed Blockade of CD47 with Bispecific Antibodies Induces Adaptive Antitumor Immunity |
title_full_unstemmed | Tumor-Directed Blockade of CD47 with Bispecific Antibodies Induces Adaptive Antitumor Immunity |
title_short | Tumor-Directed Blockade of CD47 with Bispecific Antibodies Induces Adaptive Antitumor Immunity |
title_sort | tumor-directed blockade of cd47 with bispecific antibodies induces adaptive antitumor immunity |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6698848/ https://www.ncbi.nlm.nih.gov/pubmed/31544856 http://dx.doi.org/10.3390/antib7010003 |
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