Table 1.
Therapies targeting Tregs that are FDA approved or in clinical trials.
| Therapeutic strategy | Target | Representative agents (drug type) | Clinical trial | Specific characteristics |
|---|---|---|---|---|
| Specific depletion of Treg | CD25 (IL-2Rα) | Daclizumab | FDA approved | Humanized anti-CD25 IgG1 blocking Ab |
| Basiliximab | FDA approved | Recombinant chimeric (murine/human) anti-CD25 blocking mAb | ||
| ADCT-301 | NCT03621982, NCT02432235, NCT04052997, NCT04639024, NCT02588092 | Anti-CD25 Ab (ADC conjugated) | ||
| RO7296682 | NCT04158583, NCT04642365, NCT05583617 | Anti-CD25 Ab (IL-2 non-blocking Ab) | ||
| RM-1995 | NCT05220748 | CD25-targeted near-infrared photoimmunotherapy | ||
| Denileukin diftitox | FDA approved | IL-2-diphtheria toxin fusion protein | ||
| CTLA-4 | Ipilimumab | FDA approved | Humanized anti-CTLA-4 IgG1 blocking mAb | |
| ADU-1604 | NCT03674502 | |||
| Nurulimab | NCT03472027, NCT05751928, NCT05732805 | |||
| Ticilimumab | FDA approved | Humanized anti-CTLA-4 IgG2 blocking mAb | ||
| XMAB20717 | NCT03517488 | CTLA-4 and PD-1 bispecific mAb | ||
| XMAB22841 | NCT03849469, NCT05695898 | CTLA-4 and LAG-3 bispecific mAb | ||
| ATOR-1015 | NCT03782467 | CTLA-4 and OX40 bispecific mAb | ||
| OX40 | MEDI6383 | NCT01862900, NCT02559024 | Human OX40L-IgG4 Fc fusion protein | |
| PF-04518600 | NCT03971409, NCT03390296 | Agonistic anti-OX40 mAb | ||
| BMS 986178 | NCT03831295, NCT03410901, NCT02737475 | |||
| BGB-A445 | NCT04215978, NCT06029127, NCT05661955, NCT05635708 | |||
| MEDI6469 | NCT02559024, NCT02205333, NCT01862900, NCT02274155, NCT01303705 | |||
| MOXR0916 | NCT02410512, NCT02219724, NCT03029832 | |||
| MEDI0562 | NCT03336606, NCT02705482, NCT02318394, NCT03267589 | |||
| GITR | MEDI1873 | NCT02583165 | Agonistic hexameric GITR ligand fusion protein | |
| TRX518 | NCT02628574, NCT01239134, NCT03861403 | Humanized, non-depleting, agylcosyl IgG1 mAb | ||
| MK-1248 | NCT02553499 | Agonistic humanized IgG4 mAb | ||
| BMS-986156 | NCT04021043, NCT02598960 | Agonistic humanized IgG1 mAb | ||
| GWN323 | NCT02740270 | |||
| ICOS | JTX-2011 | NCT02904226, NCT04319224, NCT03989362, NCT04549025 | Agonistic humanized IgG1 mAb | |
| KY1044 | NCT03829501 | |||
| MEDI-570 | NCT02520791 | Humanized mAb with afucosylated Fc region | ||
| GSK3359609 | NCT02723955 | Anti-ICOS Ab | ||
| XMAB23104 | NCT03752398, NCT05695898, NCT05879185 | ICOS and PD-1 bispecific mAb | ||
| Reducing recruitment of Treg | CCR4 | Mogamulizumab | FDA approved | Humanized anti-CCR4 mAb with afucosylated Fc region |
| FLX475 | NCT03674567, NCT04768686, NCT04894994 | An orally accessible and specific CCR4 antagonist | ||
| CCR8 | GS-1811 | NCT05007782 | Humanized anti-CCR8 mAb with afucosylated Fc region | |
| BAY3375968 | NCT05537740 | |||
| BMS-986340 | NCT04895709 | |||
| S-531011 | NCT05101070 | Humanized anti-CCR8 mAb | ||
| Targeting intracellular signalling | PI3Kδ | Parsaclisib | NCT02646748 | Small-molecule PI3Kδ inhibitor |
| IOA-244 | NCT04328844 | |||
| AZD8186 | NCT04001569, NCT04526470, NCT03218826, NCT01884285 | |||
| LCK | Dasatinib | FDA approved | Multi-targeted TKIs | |
| Imatinib | FDA approved | |||
| Targeting metabolic adaptation | CD36 | VT1021 | NCT03364400 | Tsp-1 and lead to Treg aptosis |
| MCT1 | AZD3965 | NCT01791595 | MCT1 inhibitor | |
| IDO | Epacadostat | FDA approved | IDO inhibitor | |
| NLG802 | NCT03164603, NCT05469490 | |||
| GDC-0919 | NCT02471846, NCT02048709, NCT05469490 | |||
| CD73 | LY3475070 | NCT04148937 | Small-molecule CD73 enzyme inhibitor | |
| CPI-006 | NCT03454451 | Anti-CD73 mAb | ||
| MEDI9447 | NCT03736473, NCT04262375 | |||
| Sym024 | NCT04672434 | |||
| CD39 | TTX-030 | NCT04306900, NCT03884556 | Anti-CD39 mAb | |
| SRF617 | NCT04336098, NCT05177770 | |||
| Targeting the tumour microenvironment | VEGF | Bevacizumab | FDA approved | Anti-VEGF mAb |
| Ramucirumab | FDA approved | Anti-VEGFR2 mAb | ||
| Sorafenib | FDA approved | Multi-target small molecule inhibitors | ||
| TGFβ | Galunisertib | NCT02423343 | TGFR1 inhibitor | |
| M7824 | FDA approved | Anti-PD-L1–TGFβ trap |
*Tregs, regulatory T cells; IL-2, interleukin 2; CTLA4, cytotoxic T lymphocyte antigen 4; CCR,C-C chemokine receptor; GITR, glucocorticoid-induced TNFR-related protein; ICOS, integrated carbon observation system; PI3Kδ,phosphoinositide 3-kinase-δ; LCK, lymphocyte-specific protein tyrosine kinase; TKI, tyrosine kinase inhibitor; Tsp-1, stimulates thrombospondin-1; MCT1, monocarboxylate transporter 1; IDO, indoleamine 2,3-dioxygenase; VEGFR2, vascular endothelial growth factor receptor 2; TGFβ, transforming growth factor-β; TGFR1, TGF-β type I receptor; TNFR, tumor necrosis factor receptor.