prikaz prve stranice dokumenta Nectin4 is a novel TIGIT ligand which combines checkpoint inhibition and tumor specificity
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Scientific paper - Original scientific paper
Nectin4 is a novel TIGIT ligand which combines checkpoint inhibition and tumor specificity
Journal for ImmunoTherapy of Cancer, 8 (2020), 1; e000266. https://doi.org/10.1136/jitc-2019-000266
Reches, Adi; Ophir, Yael; Stein, Natan; Kol, Inbal; Isaacson, Batya; Charpak Amikam, Yoav; Elnekave, Afek; Tsukerman, Pinchas; Kučan Brlić, Paola; Lenac, Tihana; Seliger, Barbara; Jonjić, Stipan; Mandelboim, Ofer

Institutional repository: Repository of the University of Rijeka, Faculty of Medicine

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Reches, A., Ophir, Y., Stein, N., Kol, I., Isaacson, B., Charpak Amikam, Y. ... Mandelboim, O. (2020). Nectin4 is a novel TIGIT ligand which combines checkpoint inhibition and tumor specificity. Journal for ImmunoTherapy of Cancer, 8. (1). doi: 10.1136/jitc-2019-000266

Reches, Adi, et al. "Nectin4 is a novel TIGIT ligand which combines checkpoint inhibition and tumor specificity." Journal for ImmunoTherapy of Cancer, vol. 8, no. 1, 2020. https://doi.org/10.1136/jitc-2019-000266

Reches, Adi, Yael Ophir, Natan Stein, Inbal Kol, Batya Isaacson, Yoav Charpak Amikam, Afek Elnekave, et al. "Nectin4 is a novel TIGIT ligand which combines checkpoint inhibition and tumor specificity." Journal for ImmunoTherapy of Cancer 8, no. 1 (2020). https://doi.org/10.1136/jitc-2019-000266

Reches, A., et al. (2020) 'Nectin4 is a novel TIGIT ligand which combines checkpoint inhibition and tumor specificity', Journal for ImmunoTherapy of Cancer, 8(1). doi: 10.1136/jitc-2019-000266

Reches A, Ophir Y, Stein N, Kol I, Isaacson B, Charpak Amikam Y, and sur.. Nectin4 is a novel TIGIT ligand which combines checkpoint inhibition and tumor specificity. Journal for ImmunoTherapy of Cancer [Internet]. 2020 June [cited 2024 November 29];8(1). doi: 10.1136/jitc-2019-000266

A. Reches, et al., "Nectin4 is a novel TIGIT ligand which combines checkpoint inhibition and tumor specificity", Journal for ImmunoTherapy of Cancer, vol. 8, no. 1, June 2020. [Online]. Available at: https://urn.nsk.hr/urn:nbn:hr:184:706583. [Accessed: 29 November 2024]

Metadata
Title (english)Nectin4 is a novel TIGIT ligand which combines checkpoint inhibition and tumor specificity
AuthorAdi Reches
AuthorYael Ophir
AuthorNatan Stein
AuthorInbal Kol
AuthorBatya Isaacson
AuthorYoav Charpak Amikam
AuthorAfek Elnekave
AuthorPinchas Tsukerman
AuthorPaola Kučan Brlić
AuthorTihana Lenac
AuthorBarbara Seliger
AuthorStipan Jonjić
AuthorOfer Mandelboim
Author's institutionUniversity of Rijeka
Faculty of Medicine
(Department of Histology and Embryology)
Scientific / art field,
discipline and subdiscipline		BIOMEDICINE AND HEALTHCARE
Basic Medical Sciences
Abstract (english)
Background The use of checkpoint inhibitors has revolutionized cancer therapy. Unfortunately, these therapies often cause immune-related adverse effects, largely due to a lack of tumor specificity. Methods We stained human natural killer cells using fusion proteins composed of the extracellular portion of various tumor markers fused to the Fc portion of human IgG1, and identified Nectin4 as a novel TIGIT ligand. Next, we generated a novel Nectin4 blocking antibody and demonstrated its efficacy as a checkpoint inhibitor in killing assays and in vivo. Results We identify Nectin4 to be a novel ligand of TIGIT. We showed that, as opposed to all other known TIGIT ligands, which bind also additional receptors, Nectin4 interacts only with TIGIT. We show that the TIGIT-Nectin4 interaction inhibits natural killer cell activity, a critical part of the innate immune response. Finally, we developed blocking Nectin4 antibodies and demonstrated that they enhance tumor killing in vitro and in vivo. Conclusion We discovered that Nectin4 is a novel ligand for TIGIT and demonstrated that specific antibodies against it enhance tumor cell killing in vitro and in vivo. Since Nectin4 is expressed almost exclusively on tumor cells, our Nectin4-blocking antibodies represent a combination of cancer specificity and immune checkpoint activity, which may prove more effective and safe for cancer immunotherapy.
Keywords (english)
Languageenglish
Publication typeScientific paper - Original scientific paper
Publication statusPublished
Peer reviewPeer review - international
Publication versionPublished version
Journal titleJournal for ImmunoTherapy of Cancer
Numberingvol. 8, no. 1, e000266
e-ISSN2051-1426
DOIhttps://doi.org/10.1136/jitc-2019-000266
URN:NBNurn:nbn:hr:184:706583
Publication2020-06
ProjectNumber: KK.011.1.01.0006
Title (english): Jačanje kapaciteta CerVirVac-a za istraživanja u virusnoj imunologiji i vakcinologiji
Leader: Stipan Jonjić
Jurisdiction: Croatia
ProjectNumber: N/A
Title (croatian): Centar izvrsnosti za virusnu imunologiju i cjepiva
Title (english): Centre of Excellence for Research in Viral Immunology and the Development of New Vaccines
Acronym: CERVirVac
Leader: Stipan Jonjić
Jurisdiction: Croatia
Funding stream: ZCI
Document URLhttps://jitc.bmj.com/lookup/doi/10.1136/jitc-2019-000266
Type of resourceText
Access conditionsOpen access
Terms of useLicence Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0) icon
Created on2020-06-25 14:37:09