Potential costimulatory molecule inhibition in aGVHD
| Target . | Reagent . | Disease setting . | Study or clinical trial status/outcome . | Clinical Trial ID . | Reference . |
|---|---|---|---|---|---|
| CD80/86 | CTLA4-Ig | GVHD prophylaxis | Phase 2, low rate of II-IV aGVHD (2 of 10 patients) | NCT01012492 | 65 |
| Phase 2 (randomized), reduced grade III/IV aGVHD and improved GFS, particularly after 7/8 MUD | NCT01743131 | 66 | |||
| CD28 | Anti-CD28 Fab Ab | NHP: GVHD prophylaxis | Preclinical, 100% GVHD-free survival in combination with sirolimus, but infection-related death is high | 68 | |
| Anti-CD28 Fab Ab | Healthy subjects | Phase 1, safe and tolerated | NCT02800811 | 69 | |
| ICOSL | Anti-ICOS ligand Ab | SLE | Phase 1b, safe, not powered for efficacy | NCT01683695 | 75 |
| CD40 | Anti-CD40 Ab | NHP: GVHD prophylaxis | Preclinical, combination with CTLA4-Ig and sirolimus, reductions in GVHD | 63 | |
| Anti-CD40 Ab | Rheumatoid arthritis | Phase 2a, safe, not powered for efficacy | NCT01751776 | 105 | |
| CD40L | Anti-CD40L Ab | GVHD prophylaxis | Phase 1/2, recruiting | NCT03605927 | |
| OX40L | Anti-OX40L Ab | NHP: GVHD prophylaxis | Preclinical, combination with sirolimus, no clinical GVHD seen | 113 | |
| Anti-OX40L Ab | Atopic dermatitis | Phase 2, recruiting | NCT03754309 | ||
| DLL4 | Anti-DLL4 Ab | NHP: GVHD prophylaxis | Preclinical, anti-DLL4 Ab monotherapy, prolonged OS | 118 |
| Target . | Reagent . | Disease setting . | Study or clinical trial status/outcome . | Clinical Trial ID . | Reference . |
|---|---|---|---|---|---|
| CD80/86 | CTLA4-Ig | GVHD prophylaxis | Phase 2, low rate of II-IV aGVHD (2 of 10 patients) | NCT01012492 | 65 |
| Phase 2 (randomized), reduced grade III/IV aGVHD and improved GFS, particularly after 7/8 MUD | NCT01743131 | 66 | |||
| CD28 | Anti-CD28 Fab Ab | NHP: GVHD prophylaxis | Preclinical, 100% GVHD-free survival in combination with sirolimus, but infection-related death is high | 68 | |
| Anti-CD28 Fab Ab | Healthy subjects | Phase 1, safe and tolerated | NCT02800811 | 69 | |
| ICOSL | Anti-ICOS ligand Ab | SLE | Phase 1b, safe, not powered for efficacy | NCT01683695 | 75 |
| CD40 | Anti-CD40 Ab | NHP: GVHD prophylaxis | Preclinical, combination with CTLA4-Ig and sirolimus, reductions in GVHD | 63 | |
| Anti-CD40 Ab | Rheumatoid arthritis | Phase 2a, safe, not powered for efficacy | NCT01751776 | 105 | |
| CD40L | Anti-CD40L Ab | GVHD prophylaxis | Phase 1/2, recruiting | NCT03605927 | |
| OX40L | Anti-OX40L Ab | NHP: GVHD prophylaxis | Preclinical, combination with sirolimus, no clinical GVHD seen | 113 | |
| Anti-OX40L Ab | Atopic dermatitis | Phase 2, recruiting | NCT03754309 | ||
| DLL4 | Anti-DLL4 Ab | NHP: GVHD prophylaxis | Preclinical, anti-DLL4 Ab monotherapy, prolonged OS | 118 |
GFS, aGVHD-free survival; MUD, matched unrelated donor; NHP, nonhuman primate; SLE, systemic lupus erythematosus.