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Blockade of the B7-H1/PD-1 Pathway for Cancer Immunotherapy

The aim of cancer immunotherapy is to treat malignant disease by inducing or enhancing cancer specific immune responses. With the identification of tumor-associated antigens (TAAs) in the 1990s, cancer immunotherapy research largely focused on inducing immune responses against TAAs but achieved limi...

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Detalles Bibliográficos
Autores principales: Flies, Dallas B., Sandler, Britt J., Sznol, Mario, Chen, Lieping
Formato: Online Artículo Texto
Lenguaje:English
Publicado: YJBM 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3238327/
https://www.ncbi.nlm.nih.gov/pubmed/22180678
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author Flies, Dallas B.
Sandler, Britt J.
Sznol, Mario
Chen, Lieping
author_facet Flies, Dallas B.
Sandler, Britt J.
Sznol, Mario
Chen, Lieping
author_sort Flies, Dallas B.
collection PubMed
description The aim of cancer immunotherapy is to treat malignant disease by inducing or enhancing cancer specific immune responses. With the identification of tumor-associated antigens (TAAs) in the 1990s, cancer immunotherapy research largely focused on inducing immune responses against TAAs but achieved limited success. More recently, the underlying mechanisms and molecular pathways that cancers manipulate to subvert immune-mediated destruction have been identified, including a set of molecules with potent coinhibitory functions. Coinhibitory molecules are expressed on the surface of immune cells, cancer cells, and stromal cells and negatively regulate immune responses to cancer. In particular, one of these ligand-receptor coinhibitory interactions, B7-H1/PD-1, is critical for modulating immune responses to cancer. This knowledge led to the design of revolutionary new immunotherapeutics based on the manipulation of these molecular pathways. Monoclonal antibodies (mAbs) are the primary immunotherapeutic modality used to promote immune function via antagonism or agonism of inhibitory or stimulatory molecular pathways, respectively. Here, we review current knowledge on the function of the B7-H1/PD-1 pathway in mice and humans, its role in the subversion of immune responses in cancer, and clinical evidence that mAb targeting of this pathway results in profound immune anti-cancer effects.
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spelling pubmed-32383272011-12-16 Blockade of the B7-H1/PD-1 Pathway for Cancer Immunotherapy Flies, Dallas B. Sandler, Britt J. Sznol, Mario Chen, Lieping Yale J Biol Med Focus: Immunology and Immunotherapeutics The aim of cancer immunotherapy is to treat malignant disease by inducing or enhancing cancer specific immune responses. With the identification of tumor-associated antigens (TAAs) in the 1990s, cancer immunotherapy research largely focused on inducing immune responses against TAAs but achieved limited success. More recently, the underlying mechanisms and molecular pathways that cancers manipulate to subvert immune-mediated destruction have been identified, including a set of molecules with potent coinhibitory functions. Coinhibitory molecules are expressed on the surface of immune cells, cancer cells, and stromal cells and negatively regulate immune responses to cancer. In particular, one of these ligand-receptor coinhibitory interactions, B7-H1/PD-1, is critical for modulating immune responses to cancer. This knowledge led to the design of revolutionary new immunotherapeutics based on the manipulation of these molecular pathways. Monoclonal antibodies (mAbs) are the primary immunotherapeutic modality used to promote immune function via antagonism or agonism of inhibitory or stimulatory molecular pathways, respectively. Here, we review current knowledge on the function of the B7-H1/PD-1 pathway in mice and humans, its role in the subversion of immune responses in cancer, and clinical evidence that mAb targeting of this pathway results in profound immune anti-cancer effects. YJBM 2011-12 2011-12 /pmc/articles/PMC3238327/ /pubmed/22180678 Text en Copyright ©2011, Yale Journal of Biology and Medicine https://creativecommons.org/licenses/by-nc/3.0/This is an open access article distributed under the terms of the Creative Commons CC BY-NC license, which permits use, distribution, and reproduction in any medium, provided the original work is properly cited. You may not use the material for commercial purposes.
spellingShingle Focus: Immunology and Immunotherapeutics
Flies, Dallas B.
Sandler, Britt J.
Sznol, Mario
Chen, Lieping
Blockade of the B7-H1/PD-1 Pathway for Cancer Immunotherapy
title Blockade of the B7-H1/PD-1 Pathway for Cancer Immunotherapy
title_full Blockade of the B7-H1/PD-1 Pathway for Cancer Immunotherapy
title_fullStr Blockade of the B7-H1/PD-1 Pathway for Cancer Immunotherapy
title_full_unstemmed Blockade of the B7-H1/PD-1 Pathway for Cancer Immunotherapy
title_short Blockade of the B7-H1/PD-1 Pathway for Cancer Immunotherapy
title_sort blockade of the b7-h1/pd-1 pathway for cancer immunotherapy
topic Focus: Immunology and Immunotherapeutics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3238327/
https://www.ncbi.nlm.nih.gov/pubmed/22180678
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