Cutting-edge: preclinical and clinical development of the first approved LAG-3 inhibitor

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dc.contributor.authorChocarro de Erauso, Luisa
dc.contributor.authorBocanegra Gondán, Ana Isabel
dc.contributor.authorBlanco, Ester
dc.contributor.authorFernández Rubio, Leticia
dc.contributor.authorArasanz Esteban, Hugo
dc.contributor.authorEchaide Górriz, Míriam
dc.contributor.authorGarnica, Maider
dc.contributor.authorRamos, Pablo
dc.contributor.authorPiñeiro Hermida, Sergio
dc.contributor.authorVera García, Ruth
dc.contributor.authorEscors Murugarren, David
dc.contributor.authorKochan, Grazyna
dc.contributor.departmentCiencias de la Saludes_ES
dc.contributor.departmentOsasun Zientziakeu
dc.contributor.funderGobierno de Navarra / Nafarroako Gobernuaes
dc.date.accessioned2022-12-30T11:58:43Z
dc.date.available2022-12-30T11:58:43Z
dc.date.issued2022
dc.date.updated2022-12-30T08:08:03Z
dc.description.abstractImmune checkpoint inhibitors (ICIs) have revolutionized medical practice in oncology since the FDA approval of the first ICI 11 years ago. In light of this, Lymphocyte-Activation Gene 3 (LAG-3) is one of the most important next-generation immune checkpoint molecules, playing a similar role as Programmed cell Death protein 1 (PD-1) and Cytotoxic T-Lymphocyte Antigen 4 (CTLA-4). 19 LAG-3 targeting molecules are being evaluated at 108 clinical trials which are demonstrating positive results, including promising bispecific molecules targeting LAG-3 simultaneously with other ICIs. Recently, a new dual anti-PD-1 (Nivolumab) and anti-LAG-3 (Relatimab) treatment developed by Bristol Myers Squibb (Opdualag), was approved by the Food and Drug Administration (FDA) as the first LAG-3 blocking antibody combination for unresectable or metastatic melanoma. This novel immunotherapy combination more than doubled median progression-free survival (PFS) when compared to nivolumab monotherapy (10.1 months versus 4.6 months). Here, we analyze the large clinical trial responsible for this historical approval (RELATIVITY-047), and discuss the preclinical and clinical developments that led to its jump into clinical practice. We will also summarize results achieved by other LAG-3 targeting molecules with promising anti-tumor activities currently under clinical development in phases I, I/II, II, and III. Opdualag will boost the entry of more LAG-3 targeting molecules into clinical practice, supporting the accumulating evidence highlighting the pivotal role of LAG-3 in cancer.en
dc.description.sponsorshipThe OncoImmunology group is funded by the Spanish Association against Cancer (AECC) [grant number PROYE16001ESCO]; Instituto de Salud Carlos III (ISCIII)-FEDER project grants [grant numbers FIS PI17/02119, FIS PI20/00010, COV20/00000, TRANSPOCART ICI19/00069]; a Biomedicine Project grant from the Department of Health of the Government of Navarre [grant number BMED 050-2019]; strategic projects from the Department of Industry, Government of Navarre (AGATA, Ref. 0011-1411-2020-000013; LINTERNA, Ref. 0011-1411-2020-000033; DESCARTHES, 0011-1411-2019-000058); European Project Horizon 2020 Improved Vaccination for Older Adults (ISOLDA; ID: 848166); Crescendo Biologics Ltd. supported the OncoImmunology group for the development and testing of PD-1 and LAG-3 bispecifics.en
dc.format.mimetypeapplication/pdfen
dc.format.mimetypeapplication/zipen
dc.identifier.citationChocarro-de-Erauso, L.; Bocanegra, A.; Blanco, E.; Fernández-Rubio, L.; Arasanz-Esteban, H.; Echaide-Gorriz, M.; Garnica, M.; Ramos, P.; Piñeiro-Hermida, S.; Vera, R.; Escors, D.; Kochan, G.. (2022). Cutting-edge: preclinical and clinical development of the first approved LAG-3 inhibitor. Cells. 11,15 1-24 .en
dc.identifier.doi10.3390/cells11152351
dc.identifier.issn2073-4409
dc.identifier.urihttps://academica-e.unavarra.es/handle/2454/44509
dc.language.isoengen
dc.publisherMDPIen
dc.relation.ispartofCells, 11, 2351en
dc.relation.projectIDinfo:eu-repo/grantAgreement/ISCIII/Plan Estatal de Investigación Científica y Técnica y de Innovación 2013-2016 (ISCIII)/PI17%2F02119/ES/
dc.relation.projectIDinfo:eu-repo/grantAgreement/ISCIII/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020 (ISCIII)/PI20%2F00010/ES/
dc.relation.projectIDinfo:eu-repo/grantAgreement/European Commission/Horizon 2020 Framework Programme/848166/
dc.relation.publisherversionhttps://doi.org/10.3390/cells11152351
dc.rights© 2022 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) licenseen
dc.rights.accessRightsinfo:eu-repo/semantics/openAccess
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.subjectBMS-986016en
dc.subjectLAG-3en
dc.subjectNivolumaben
dc.subjectOpdualagen
dc.subjectPD-1en
dc.subjectRelatimaben
dc.titleCutting-edge: preclinical and clinical development of the first approved LAG-3 inhibitoren
dc.typeinfo:eu-repo/semantics/article
dc.type.versioninfo:eu-repo/semantics/publishedVersion
dspace.entity.typePublication
relation.isAuthorOfPublicationfe5c362e-3c0c-4edb-aa2e-0de27c815ad2
relation.isAuthorOfPublication.latestForDiscoveryfe5c362e-3c0c-4edb-aa2e-0de27c815ad2

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