Therapeutic potential of targeting LAG-3 in cancer
Immune checkpoint inhibitors targeting negative regulatory checkpoints including programmed death-1 (PD-1) and cytotoxic T-lymphocyte-associated protein 4 have produced significant improvements in progression-free survival (PFS) and overall survival in multiple solid tumors. Lymphocyte activation ge...
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| Format: | Article |
| Language: | English |
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BMJ Publishing Group
2025-07-01
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| Series: | Journal for ImmunoTherapy of Cancer |
| Online Access: | https://jitc.bmj.com/content/13/7/e011652.full |
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| _version_ | 1850116621243252736 |
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| author | Diwakar Davar Ana Carrizosa Anderson Ivan Diaz-Padilla |
| author_facet | Diwakar Davar Ana Carrizosa Anderson Ivan Diaz-Padilla |
| author_sort | Diwakar Davar |
| collection | DOAJ |
| description | Immune checkpoint inhibitors targeting negative regulatory checkpoints including programmed death-1 (PD-1) and cytotoxic T-lymphocyte-associated protein 4 have produced significant improvements in progression-free survival (PFS) and overall survival in multiple solid tumors. Lymphocyte activation gene 3 (LAG-3) is an inhibitory receptor that is highly expressed by exhausted T cells. Dual blockade of LAG-3 and PD-1 with monoclonal antibodies relatlimab and nivolumab has improved PFS in advanced melanoma, leading to Food and Drug Administration approval for this indication. Concurrently, enthusiasm for targeting LAG-3 has been tempered by negative results in multiple indications, although novel approaches including LAG-3-directed bispecifics tebotelimab continue to demonstrate promise. In this review, we discuss the current understanding of LAG-3 in regulating antitumor immunity and the ongoing state of clinical development of LAG-3-directed agents in cancer. |
| format | Article |
| id | doaj-art-6c83ebef901f42569cb2d812758aa866 |
| institution | OA Journals |
| issn | 2051-1426 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | BMJ Publishing Group |
| record_format | Article |
| series | Journal for ImmunoTherapy of Cancer |
| spelling | doaj-art-6c83ebef901f42569cb2d812758aa8662025-08-20T02:36:16ZengBMJ Publishing GroupJournal for ImmunoTherapy of Cancer2051-14262025-07-0113710.1136/jitc-2025-011652Therapeutic potential of targeting LAG-3 in cancerDiwakar Davar0Ana Carrizosa Anderson1Ivan Diaz-Padilla2Department of Medicine, UPMC Hillman Cancer Center, Pittsburgh, Pennsylvania, USAHarvard Medical School, Boston, Massachusetts, USAOncology Global Clinical Development, GSK, Baar, SwitzerlandImmune checkpoint inhibitors targeting negative regulatory checkpoints including programmed death-1 (PD-1) and cytotoxic T-lymphocyte-associated protein 4 have produced significant improvements in progression-free survival (PFS) and overall survival in multiple solid tumors. Lymphocyte activation gene 3 (LAG-3) is an inhibitory receptor that is highly expressed by exhausted T cells. Dual blockade of LAG-3 and PD-1 with monoclonal antibodies relatlimab and nivolumab has improved PFS in advanced melanoma, leading to Food and Drug Administration approval for this indication. Concurrently, enthusiasm for targeting LAG-3 has been tempered by negative results in multiple indications, although novel approaches including LAG-3-directed bispecifics tebotelimab continue to demonstrate promise. In this review, we discuss the current understanding of LAG-3 in regulating antitumor immunity and the ongoing state of clinical development of LAG-3-directed agents in cancer.https://jitc.bmj.com/content/13/7/e011652.full |
| spellingShingle | Diwakar Davar Ana Carrizosa Anderson Ivan Diaz-Padilla Therapeutic potential of targeting LAG-3 in cancer Journal for ImmunoTherapy of Cancer |
| title | Therapeutic potential of targeting LAG-3 in cancer |
| title_full | Therapeutic potential of targeting LAG-3 in cancer |
| title_fullStr | Therapeutic potential of targeting LAG-3 in cancer |
| title_full_unstemmed | Therapeutic potential of targeting LAG-3 in cancer |
| title_short | Therapeutic potential of targeting LAG-3 in cancer |
| title_sort | therapeutic potential of targeting lag 3 in cancer |
| url | https://jitc.bmj.com/content/13/7/e011652.full |
| work_keys_str_mv | AT diwakardavar therapeuticpotentialoftargetinglag3incancer AT anacarrizosaanderson therapeuticpotentialoftargetinglag3incancer AT ivandiazpadilla therapeuticpotentialoftargetinglag3incancer |