Clinical landscape of LAG-3-targeted therapy

Lymphocyte-activated gene 3 (LAG-3) is a cell surface inhibitory receptor and a key regulator of immune homeostasis with multiple biological activities related to T-cell functions. LAG-3 is considered a next-generation immune checkpoint of clinical importance, right next to programmed cell death pro...

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Detalhes bibliográficos
Autores: Chocarro de Erauso, Luisa, Blanco, Ester, Arasanz Esteban, Hugo, Fernández Rubio, Leticia, Bocanegra Gondán, Ana Isabel, Echaide Górriz, Míriam, Garnica, Maider, Ramos, Pablo, Fernández Hinojal, Gonzalo, Vera García, Ruth, Kochan, Grazyna, Escors Murugarren, David
Formato: artículo
Estado:Versión publicada
Fecha de publicación:2022
País:España
Recursos:Universidad Pública de Navarra
Repositorio:Academica-e. Repositorio Institucional de la Universidad Pública de Navarra
OAI Identifier:oai:academica-e.unavarra.es:2454/44807
Acesso em linha:https://hdl.handle.net/2454/44807
Access Level:acceso abierto
Palavra-chave:Cancer treatment
Immune checkpoint
Immunotherapy
LAG-3
Targeted therapy
Descrição
Resumo:Lymphocyte-activated gene 3 (LAG-3) is a cell surface inhibitory receptor and a key regulator of immune homeostasis with multiple biological activities related to T-cell functions. LAG-3 is considered a next-generation immune checkpoint of clinical importance, right next to programmed cell death protein 1 (PD-1) and cytotoxic T-cell lymphocyte antigen-4 (CTLA-4). Indeed, it is the third inhibitory receptor to be exploited in human anticancer immunotherapies. Several LAG-3-antagonistic immunotherapies are being evaluated at various stages of preclinical and clinical development. In addition, combination therapies blocking LAG-3 together with other immune checkpoints are also being evaluated at preclinical and clinical levels. Indeed, the co-blockade of LAG-3 with PD-1 is demonstrating encouraging results. A new generation of bispecific PD-1/LAG-3-blocking agents have also shown strong capacities to specifically target PD-1+ LAG-3+ highly dysfunctional T cells and enhance their proliferation and effector activities. Here we identify and classify preclinical and clinical trials conducted involving LAG-3 as a target through an extensive bibliographic research. The current understanding of LAG-3 clinical applications is summarized, and most of the publically available data up to date regarding LAG-3-targeted therapy preclinical and clinical research and development are reviewed and discussed.