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Checkpoint antibodies in this group block inhibitory immune receptors other than PD-1 on T cells and other lymphocytes. Ipilimumab and tremelimumab bind cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and prevent its competition with CD28 for B7 ligands. Relatlimab targets lymphocyte-activation gene 3 (LAG-3), and tiragolumab targets T-cell immunoreceptor with Ig and ITIM domains (TIGIT). Sabatolimab and cobolimab bind T-cell immunoglobulin and mucin-domain containing-3 (TIM-3) on T cells and myeloid cells. Further antibodies cover B7-H3, B7-H4, VISTA, BTLA, PVRIG and the adenosine-pathway enzymes CD39 and CD73.
Synonyms: OMP-313M32
Etigilimab is a humanized IgG1 monoclonal antibody that blocks the interaction between TIGIT and its ligand CD155 (PVR), a key pathway in immune checkpoint regulation. By inhibiting TIGIT signaling, Etigilimab enhances T cell–mediated immune responses and is widely used in tumor immunology research and checkpoint blockade studies.
Synonyms: JTX 8064
Polzastobart (JTX-8064) is a humanized IgG4 monoclonal antibody that functions as an antagonist by selectively targeting and binding to LILRB2. This interaction inhibits LILRB2 from associating with its natural ligands, including both classical and non-classical MHC class I molecules. By preventing LILRB2 from binding to HLA-A/B and HLA-G, which are markers of immunotolerance on tumor cells, Polzastobart effectively disrupts this inhibitory signal and enhances the production of pro-inflammatory cytokines in macrophages. This mechanism classifies Polzastobart as a macrophage immune checkpoint inhibitor, making it a critical tool in cancer immunotherapy research.
Synonyms: LAG525; IMP701
Ieramilimab (LAG525; IMP701) is a humanized IgG4 monoclonal antibody designed to target and bind to lymphocyte-activation gene 3 (LAG-3). This interaction effectively inhibits the binding of LAG-3 to major histocompatibility complex class II (MHC-II) molecules, which is critical in modulating immune response. Ieramilimab is utilized extensively in research focused on immune checkpoint regulation and potential therapeutic interventions for various immunological disorders.
Synonyms: JS004
Tifcemalimab (JS004) is a humanized monoclonal antibody that targets BTLA (B and T lymphocyte attenuator), a key regulator in the immune checkpoint pathway. By binding specifically to BTLA, Tifcemalimab effectively inhibits the interaction between BTLA and its ligand HVEM, thereby blocking the BTLA-mediated inhibitory signaling pathway. This antibody is primarily utilized in cancer research to study the modulation of immune responses against tumor cells.
Synonyms: MK-4280
Favezelimab (MK-4280) is a humanized monoclonal antibody targeting LAG-3, designed to inhibit the binding of LAG-3 to MHC class II molecules. This interaction blockade enhances T-cell function and may potentiate an anti-tumor immune response. Favezelimab is primarily investigated for its therapeutic potential in colorectal cancer research, particularly in combination with the PD-L1 inhibitor Pembrolizumab, to synergistically enhance immune-mediated tumor suppression.
Synonyms: BMS-986016
Relatlimab (BMS-986016) is a human monoclonal antibody targeting LAG-3, developed through the immunization of transgenic mice engineered to express human immunoglobulin miniloci, using recombinant LAG-3 protein. This antibody effectively inhibits the interaction between LAG-3 and MHC II with an IC50 of 0.67 nM, and between LAG-3 and FGL1 with an IC50 of 0.019 nM. It is primarily utilized in cancer research, providing a valuable tool for investigating the role of LAG-3 in tumor immune evasion and potential therapeutic interventions.
Synonyms: BI-754111
Miptenalimab (BI-754111) is a monoclonal antibody targeting human LAG-3 with a dissociation constant (K_D) of 88.6 nM. This antibody effectively inhibits the interaction between LAG-3 and its physiological ligand MHC class II, highlighting its potential utility in modulating immune responses in oncological and immunological research.
