TABLE 1.
Overview of novel immune checkpoints.
| Immune checkpoints | LAG-3 | TIGIT | TIM-3 | B7-H3 | VISTA | ICOS | BTLA |
|---|---|---|---|---|---|---|---|
| Other names | CD223 | Vstm3, Vsig9, WUCAM | HAVCR2 | CD276 | Dies1, DD1, Gi24, B7-H5, PD-1H | CD278 | CD272 |
| Function | Co-inhibition | Co-inhibition | Co-inhibition | Co-inhibition or co-stimulation | Co-inhibition | Co-inhibition or co-stimulation | Co-inhibition or co-stimulation |
| Cells that express the immune checkpoints | NK cells, DC, activated T cells, Tregs, B cells, | NK cells, T cells | NK cells, DCs, activated T cells, Tregs, B cells, monocytes, cancer cells | NK cells, DCs, activated T cells, monocytes, cancer cells | T cells, myeloid cells | Activated T cells | Mature T cells, Tregs, B cells, macrophages |
| Ligands or receptors | MHC-II, galectin-3, LSECtin, a-synuclein, FGL1 | CD155, CD112 | HMGB-1, galectin-9, ceacam-1, PtdSer | Unknown | VSIG-3 | ICOSL | HVEM, LIGHT, lymphotoxin- |
| Immune checkpoint agents | APC activator, anti-LAG3 mAb, LAG3 and PD1 DART protein, LAG3 fusion protein, bispecific Ab to both LAG3 and PD-L1 | Anti-TIGIT mAb | Anti-TIM-3 mAb, anti-PD-1/TIM3 bispecific Ab | Anti-B7-H3 mAb, B7-H3-targeting ADC, radiolabeled anti-B7-H3 mAb, CAR T-cell therapy | Anti-VISTA mAb, small molecule VISTA | Anti-ICOS agonist, anti-ICOS antagonist | |
| No. of investigational agents | 17 | 10 | 8 | 11 | 3 | 4 | 4 |
| Clinical trials | |||||||
| Phase 1 | Completed (eftilagimod alpha, BI 754111, Sym022, INCAGN02385), ongoing | Ongoing | Completed (Sym023), ongoing | Completed (enoblituzumab), ongoing | Completed (CA-170), ongoing | Ongoing | Completed (JTX-2011), ongoing |
| Phase 2 | Completed (eftilagimod alpha, LAG525), ongoing | Ongoing | Ongoing | Ongoing | NA | NA | NA |
| Phase 3 | Ongoing (MGD013) | Ongoing (tiragolumab) | Ongoing (sabatolimab) | Ongoing | NA | NA | NA |
| Combination treatment | Yes | Yes | Yes | Yes | No | Yes | Yes |
| Other immune checkpoint inhibitors | Yes | Yes | Yes | Yes | Yes | Yes | |
| Targeted agents | Yes | Yes | Yes | Yes | Yes | Yes | |
| Chemotherapy | Yes | Yes | Yes | Yes | Yes | No | |
| Radiotherapy | Yes | No | No | Yes | No | No |
Abbreviations: APC, antigen presenting cell; BTLA, B and T-lymphocyte attenuator; CAR-T, chimeric antigen receptor T cell; DART, dual-affinity re-targeting proteins; DCs, dendritic cells; Dies 1, differentiation of embryonic stem cells 1; HAVCR2, hepatitis A virus cellular receptor 2; HVEM, herpes-virus entry mediator; mAb, monoclonal antibody; ICOS, Inducible T cell costimulator; ICOSL, Inducible T cell costimulatory ligand; LAG-3, lymphocyte-associated gene 3; NK cells, natural killer cells; PD-1H, PD-1 homologue; PD-L1, programmed death-ligand 1; PtdSer, phosphatidyl serine; T regs, ceacam-1, carcinoembryonic antigen cell adhesion molecule 1; T regs, regulatory T cells; TIGIT, T cell immunoglobulin and ITIM domain; TIM-3, T-cell immunoglobulin and mucin domain-3; VISTA, V-domain immunoglobulin suppressor of T cell activation; VSIG-3, V-Set and Immunoglobulin domain containing 3; WUCAM, Washington University cell adhesion molecule.