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Cutting-edge: preclinical and clinical development of the first approved LAG-3 inhibitor
dc.creator | Chocarro, Luisa | es_ES |
dc.creator | Bocanegra Gondán, Ana Isabel | es_ES |
dc.creator | Blanco, Ester | es_ES |
dc.creator | Fernández Rubio, Leticia | es_ES |
dc.creator | Arasanz Esteban, Hugo | es_ES |
dc.creator | Echaide Górriz, Míriam | es_ES |
dc.creator | Garnica, Maider | es_ES |
dc.creator | Ramos, Pablo | es_ES |
dc.creator | Piñeiro Hermida, Sergio | es_ES |
dc.creator | Vera García, Ruth | es_ES |
dc.creator | Escors Murugarren, David | es_ES |
dc.creator | Kochan, Grazyna | es_ES |
dc.date.accessioned | 2022-12-30T11:58:43Z | |
dc.date.available | 2022-12-30T11:58:43Z | |
dc.date.issued | 2022 | |
dc.identifier.citation | Chocarro-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.issn | 2073-4409 | |
dc.identifier.uri | https://hdl.handle.net/2454/44509 | |
dc.description.abstract | Immune 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.sponsorship | The 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.mimetype | application/pdf | en |
dc.format.mimetype | application/zip | en |
dc.language.iso | eng | en |
dc.publisher | MDPI | en |
dc.relation.ispartof | Cells, 11, 2351 | en |
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) license | en |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | |
dc.subject | BMS-986016 | en |
dc.subject | LAG-3 | en |
dc.subject | Nivolumab | en |
dc.subject | Opdualag | en |
dc.subject | PD-1 | en |
dc.subject | Relatimab | en |
dc.title | Cutting-edge: preclinical and clinical development of the first approved LAG-3 inhibitor | en |
dc.type | Artículo / Artikulua | es |
dc.type | info:eu-repo/semantics/article | en |
dc.date.updated | 2022-12-30T08:08:03Z | |
dc.contributor.department | Ciencias de la Salud | es_ES |
dc.contributor.department | Osasun Zientziak | eu |
dc.rights.accessRights | Acceso abierto / Sarbide irekia | es |
dc.rights.accessRights | info:eu-repo/semantics/openAccess | en |
dc.identifier.doi | 10.3390/cells11152351 | |
dc.relation.projectID | info:eu-repo/grantAgreement/ISCIII/Plan Estatal de Investigación Científica y Técnica y de Innovación 2013-2016 (ISCIII)/PI17%2F02119/ES/ | en |
dc.relation.projectID | info:eu-repo/grantAgreement/ISCIII/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020 (ISCIII)/PI20%2F00010/ES/ | en |
dc.relation.projectID | info:eu-repo/grantAgreement/European Commission/Horizon 2020 Framework Programme/848166 | en |
dc.relation.publisherversion | https://doi.org/10.3390/cells11152351 | |
dc.type.version | Versión publicada / Argitaratu den bertsioa | es |
dc.type.version | info:eu-repo/semantics/publishedVersion | en |
dc.contributor.funder | Gobierno de Navarra / Nafarroako Gobernua | es |