LAG-3, TIGIT & TIM-3: Next-Generation Checkpoint Targets for Immunotherapy Research

As PD-1/PD-L1 and CTLA-4 therapies mature, the next wave of checkpoint targets — LAG-3, TIGIT, and TIM-3 — is advancing rapidly through clinical development. For a complete overview of all checkpoint targets, see our Immune Checkpoint Inhibitors guide.

Target Biology and Clinical Relevance

LAG-3 (CD223) binds MHC class II and FGL1, inhibiting T cell proliferation and cytokine production. Relatlimab (anti-LAG-3) combined with nivolumab was approved for melanoma in 2022, validating LAG-3 as the third clinically proven checkpoint target.

TIGIT binds CD155 (PVR) and CD112, competing with the activating receptor CD226. TIGIT is expressed on exhausted CD8+ T cells and NK cells. Tiragolumab (anti-TIGIT) is in Phase III trials for NSCLC and other solid tumors.

TIM-3 (HAVCR2) binds galectin-9, CEACAM1, and phosphatidylserine. Co-expression of PD-1 and TIM-3 on CD8+ T cells defines the most deeply exhausted T cell subset. Anti-TIM-3 antibodies (cobolimab, sabatolimab) are in clinical development as combination partners for anti-PD-1. Research biosimilar versions of relatlimab and other next-gen checkpoint antibodies are available for preclinical studies.

For research: multi-parameter flow cytometry panels combining PD-1, LAG-3, TIGIT, TIM-3, and CD39 on CD8+ T cells are the standard approach for characterizing T cell exhaustion states in the tumor microenvironment. abinScience offers detection antibodies in multiple conjugate formats for panel design. For step-by-step staining protocols and gating strategies, see our Flow Cytometry for TIL Analysis guide.

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References

1. Pardoll DM. The blockade of immune checkpoints in cancer immunotherapy. Nat Rev Cancer. 2012;12(4):252-264. doi: 10.1038/nrc3239

2. Topalian SL, Drake CG, Pardoll DM. Immune checkpoint blockade: a common denominator approach to cancer therapy. Cancer Cell. 2015;27(4):450-461. doi: 10.1016/j.ccell.2015.03.001

3. Wei SC, Duffy CR, Allison JP. Fundamental mechanisms of immune checkpoint blockade therapy. Cancer Discov. 2018;8(9):1069-1086. doi: 10.1158/2159-8290.CD-18-0367

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