Restoration of T-cell Effector Function, Depletion of Tregs, and Direct Killing of Tumor Cells: The Multiple Mechanisms of Action of a-TIGIT Antagonist Antibodies
dc.rights.license | open | en_US |
dc.contributor.author | PREILLON, Julie | |
dc.contributor.author | CUENDE, Julia | |
dc.contributor.author | RABOLLI, Virginie | |
dc.contributor.author | GARNERO, Lucile | |
dc.contributor.author | MERCIER, Marjorie | |
dc.contributor.author | WALD, Noemie | |
hal.structure.identifier | Immunology from Concept and Experiments to Translation = Immunologie Conceptuelle, Expérimentale et Translationnelle [ImmunoConcept] | |
dc.contributor.author | PAPPALARDO, Angela | |
dc.contributor.author | DENIES, Sofie | |
dc.contributor.author | JAMART, Diane | |
dc.contributor.author | MICHAUX, Anne-Catherine | |
dc.contributor.author | PIRSON, Romain | |
hal.structure.identifier | Immunology from Concept and Experiments to Translation = Immunologie Conceptuelle, Expérimentale et Translationnelle [ImmunoConcept] | |
dc.contributor.author | PITARD, Vincent | |
dc.contributor.author | BAGOT, Martine | |
dc.contributor.author | PRASAD, Shruthi | |
dc.contributor.author | HOUTHUYS, Erica | |
dc.contributor.author | BROUWER, Margreet | |
dc.contributor.author | MARILLIER, Reece | |
dc.contributor.author | LAMBOLEZ, Florence | |
dc.contributor.author | MARCHANTE, Joao R. | |
dc.contributor.author | NYAWOUAME, Florence | |
dc.contributor.author | CARTER, Mathew J. | |
dc.contributor.author | BARON-BODO, Veronique | |
dc.contributor.author | MARIE-CARDINE, Anne | |
dc.contributor.author | CRAGG, Mark | |
hal.structure.identifier | Immunology from Concept and Experiments to Translation = Immunologie Conceptuelle, Expérimentale et Translationnelle [ImmunoConcept] | |
dc.contributor.author | DECHANET-MERVILLE, Julie
IDREF: 061667994 | |
dc.contributor.author | DRIESSENS, Gregory | |
dc.contributor.author | HOOFD, Catherine | |
dc.date.accessioned | 2022-10-11T13:37:37Z | |
dc.date.available | 2022-10-11T13:37:37Z | |
dc.date.created | 2020-12-04 | |
dc.date.issued | 2020-12-04 | |
dc.identifier.issn | 1535-7163 (Print) 1538-8514 (Electronic) 1535-7163 (Linking) | en_US |
dc.identifier.other | http://mct.aacrjournals.org/content/suppl/2021/01/09/1535-7163.MCT-20-0464.DC1 | en_US |
dc.identifier.uri | https://oskar-bordeaux.fr/handle/20.500.12278/148380 | |
dc.description.abstractEn | TIGIT is an immune checkpoint inhibitor expressed by effector CD4þ and CD8þ T cells, NK cells, and regulatory T cells (Tregs). Inhibition of TIGIT-ligand binding using antagonistic anti-TIGIT mAbs has shown in vitro potential to restore T-cell function and therapeutic efficacy in murine tumor models when combined with an anti–PD(L)-1 antibody. In the current work, we demonstrate broader TIGIT expression than previously reported in healthy donors and patients with cancer with expression on gd T cells, particularly in CMV-seropositive donors, and on tumor cells from hematologic malignancies. Quantification of TIGIT density revealed tumor-infiltrating Tregs as the population expressing the highest receptor density. Consequently, the therapeutic potential of anti-TIGIT mAbs might be wider than the previously described anti–PD(L)-1-like restoration of ab T-cell function. CD155 also mediated inhibition of gd T cells, an immune population not previously described to be sensitive to TIGIT inhibition, which could be fully prevented via use of an antagonistic anti-TIGIT mAb (EOS-448). In PBMCs from patients with cancer, as well as in tumor-infiltrating lymphocytes from mice, the higher TIGIT expression in Tregs correlated with strong antibody-dependent killing and preferential depletion of this highly immunosuppressive population. Accordingly, the ADCC/ADCP–enabling format of the anti-TIGIT mAb had superior antitumor activity, which was dependent upon Fcg receptor engagement. In addition, the anti-TIGIT mAb was able to induce direct killing of TIGITexpressing tumor cells both in human patient material and in animal models, providing strong rationale for therapeutic intervention in hematologic malignancies. These findings reveal multiple therapeutic opportunities for anti-TIGIT mAbs in cancer therapeutics. | |
dc.language.iso | EN | en_US |
dc.rights | Attribution-NonCommercial-NoDerivs 3.0 United States | * |
dc.rights.uri | http://creativecommons.org/licenses/by-nc-nd/3.0/us/ | * |
dc.subject.en | Animals | |
dc.subject.en | Antibodies : Monoclonal / immunology | |
dc.subject.en | Antibodies : Neoplasm / immunology | |
dc.subject.en | Antibodies : Neoplasm / pharmacology | |
dc.subject.en | Antibody-Dependent Cell Cytotoxicity / drug effects | |
dc.subject.en | Antigens : CD / metabolism | |
dc.subject.en | Cytotoxicity : Immunologic / drug effects | |
dc.subject.en | Female | |
dc.subject.en | Healthy Volunteers | |
dc.subject.en | Humans | |
dc.subject.en | Immunoglobulin G / metabolism | |
dc.subject.en | Lymphocyte Depletion | |
dc.subject.en | Lymphocytes : Tumor-Infiltrating / drug effects | |
dc.subject.en | Lymphocytes : Tumor-Infiltrating / immunology | |
dc.subject.en | Mice : Inbred BALB C | |
dc.subject.en | Mice : Inbred C57BL | |
dc.subject.en | Receptors : Antigen : T-Cell : gamma-delta / metabolism | |
dc.subject.en | Receptors : IgG / metabolism | |
dc.subject.en | Receptors : Immunologic / antagonists & inhibitors | |
dc.subject.en | Receptors : Immunologic / metabolism | |
dc.subject.en | T-Lymphocytes : Regulatory / drug effects | |
dc.subject.en | T-Lymphocytes : Regulatory / immunology | |
dc.title.en | Restoration of T-cell Effector Function, Depletion of Tregs, and Direct Killing of Tumor Cells: The Multiple Mechanisms of Action of a-TIGIT Antagonist Antibodies | |
dc.title.alternative | Mol Cancer Ther | en_US |
dc.type | Article de revue | en_US |
dc.identifier.doi | 10.1158/1535-7163.MCT-20-0464 | en_US |
dc.subject.hal | Sciences du Vivant [q-bio]/Immunologie | en_US |
dc.identifier.pubmed | 33277440 | en_US |
bordeaux.journal | Molecular Cancer Therapeutics | en_US |
bordeaux.page | 121-131 | en_US |
bordeaux.volume | 20 | en_US |
bordeaux.hal.laboratories | ImmunoConcEpT - UMR 5164 | en_US |
bordeaux.issue | 1 | en_US |
bordeaux.institution | Université de Bordeaux | en_US |
bordeaux.institution | CNRS | en_US |
bordeaux.peerReviewed | oui | en_US |
bordeaux.inpress | non | en_US |
hal.export | false | |
workflow.import.source | pubmed | |
dc.rights.cc | CC BY-NC-ND | en_US |
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