Global survey of the immunomodulatory potential of common drugs.
Small molecule drugs may complement antibody-based therapies in an immune-oncology setting, yet systematic methods for the identification and characterization of the immunomodulatory properties of these entities are lacking. We surveyed the immumomodulatory potential of 1,402 small chemical molecule...
| Autores principales: | , , , , , , , , , , , , , , , |
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| Formato: | Journal article |
| Lenguaje: | English |
| Publicado: |
Nature Publishing Group
2017
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| _version_ | 1826292300249038848 |
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| author | Vladimer, G Snijder, B Krall, N Bigenzahn, J Huber, K Lardeau, C Sanjiv, K Ringler, A Berglund, U Sabler, M de la Fuente, O Knöbl, P Kubicek, S Helleday, T Jäger, U Superti-Furga, G |
| author_facet | Vladimer, G Snijder, B Krall, N Bigenzahn, J Huber, K Lardeau, C Sanjiv, K Ringler, A Berglund, U Sabler, M de la Fuente, O Knöbl, P Kubicek, S Helleday, T Jäger, U Superti-Furga, G |
| author_sort | Vladimer, G |
| collection | OXFORD |
| description | Small molecule drugs may complement antibody-based therapies in an immune-oncology setting, yet systematic methods for the identification and characterization of the immunomodulatory properties of these entities are lacking. We surveyed the immumomodulatory potential of 1,402 small chemical molecules as defined by their ability to alter the cell-cell interactions among peripheral mononuclear leukocytes ex vivo, using automated microscopy and population-wide single-cell image analysis. Surprisingly, some 10% of the agents tested affected these cell-cell interactions differentially. The results accurately recapitulated known immunomodulatory drug classes, and revealed several clinically approved drugs that unexpectedly harbor the ability to modulate the immune system, potentially contributing to their physiological mechanism of action. For instance, the kinase inhibitor crizotinib promoted T-cell interactions with monocytes as well as with cancer cells, through inhibition of MST1R/RON (macrophage-stimulating protein receptor) and subsequent upregulation of MHC (major histocompatibility complex) expression. The approach offers an attractive platform for the personalized identification and characterization of immunomodulatory therapeutics. |
| first_indexed | 2024-03-07T03:12:33Z |
| format | Journal article |
| id | oxford-uuid:b4ae43d2-743e-4281-9030-447a6dc569f2 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T03:12:33Z |
| publishDate | 2017 |
| publisher | Nature Publishing Group |
| record_format | dspace |
| spelling | oxford-uuid:b4ae43d2-743e-4281-9030-447a6dc569f22022-03-27T04:28:06ZGlobal survey of the immunomodulatory potential of common drugs.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:b4ae43d2-743e-4281-9030-447a6dc569f2EnglishSymplectic Elements at OxfordNature Publishing Group2017Vladimer, GSnijder, BKrall, NBigenzahn, JHuber, KLardeau, CSanjiv, KRingler, ABerglund, USabler, Mde la Fuente, OKnöbl, PKubicek, SHelleday, TJäger, USuperti-Furga, GSmall molecule drugs may complement antibody-based therapies in an immune-oncology setting, yet systematic methods for the identification and characterization of the immunomodulatory properties of these entities are lacking. We surveyed the immumomodulatory potential of 1,402 small chemical molecules as defined by their ability to alter the cell-cell interactions among peripheral mononuclear leukocytes ex vivo, using automated microscopy and population-wide single-cell image analysis. Surprisingly, some 10% of the agents tested affected these cell-cell interactions differentially. The results accurately recapitulated known immunomodulatory drug classes, and revealed several clinically approved drugs that unexpectedly harbor the ability to modulate the immune system, potentially contributing to their physiological mechanism of action. For instance, the kinase inhibitor crizotinib promoted T-cell interactions with monocytes as well as with cancer cells, through inhibition of MST1R/RON (macrophage-stimulating protein receptor) and subsequent upregulation of MHC (major histocompatibility complex) expression. The approach offers an attractive platform for the personalized identification and characterization of immunomodulatory therapeutics. |
| spellingShingle | Vladimer, G Snijder, B Krall, N Bigenzahn, J Huber, K Lardeau, C Sanjiv, K Ringler, A Berglund, U Sabler, M de la Fuente, O Knöbl, P Kubicek, S Helleday, T Jäger, U Superti-Furga, G Global survey of the immunomodulatory potential of common drugs. |
| title | Global survey of the immunomodulatory potential of common drugs. |
| title_full | Global survey of the immunomodulatory potential of common drugs. |
| title_fullStr | Global survey of the immunomodulatory potential of common drugs. |
| title_full_unstemmed | Global survey of the immunomodulatory potential of common drugs. |
| title_short | Global survey of the immunomodulatory potential of common drugs. |
| title_sort | global survey of the immunomodulatory potential of common drugs |
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