Outcome of interference with murine coinhibitory molecules
| Molecule . | Therapy . | Tumor . | Outcome . | Reference . |
|---|---|---|---|---|
| Autologous | ||||
| CTLA-4 | Anti–CTLA-4 + ova-DC vaccination | Thymoma | Improved tumor rejection, enhanced antigen-specific T-cell responses | 23 |
| CTLA-4 | Anti–CTLA-4; CTLA-4 deletional knockout | AML | Increased survival and improved tumor rejection | 22 |
| CTLA-4 | Anti–CTLA-4 | AML | Enhanced T-cell response, prolonged survival | 54 |
| PD-1 | Anti–PD-L1; PD-1 knockout | MM | Delayed tumor growth; complete tumor rejection in PD-1 knockout | 49 |
| PD-1 | HSCT + whole cell vaccination + anti–PD-L1 | MM | Increased survival | 52 |
| PD-1 | Anti–PD-L1; PD-1 knockout | AML | Enhanced T-cell response, improved tumor rejection, increased survival | 50 |
| PD-1/TIM-3 | Anti–PD-L1 and/or mTim-3 hFc | AML | Delayed tumor growth on monotherapy, improved tumor rejection on combined blockade | 93 |
| CD200 | Anti-CD200 | AML | Increased survival | 86 |
| CD200 | Anti-CD200 | B-CLL | Improved tumor rejection | 87 |
| CD200 | Anti-CD200 | B-cell lymphoma | Delayed tumor growth | 88 |
| Allogeneic | ||||
| CTLA-4 | Anti–CTLA-4 | AML | Enhanced T-cell response and GVHD early after BMT; enhanced tumor-specific T-cell response later after BMT with low GVHD | 28 |
| PD-1 | Anti–PD-L1 | Lymphoma | Enhanced T-cell response | 63 |
| PD-1 | Anti–PD-L1 | None | Enhanced alloreactive T-cell response, no GVHD | 64 |
| PD-1 | Anti–PD-L1; PD-1 knockout | CML | Increased survival | 65 |
| BTLA | BTLA agonist | B-cell lymphoma | Early after BMT: prevention of GVHD; later after BMT: no effect on GVHD; effective GVT response | 78 |
| BTLA | BTLA agonist | Mastocytoma/T-cell lymphoma | Inhibition of alloreactive T-cell response, prevention from GVHD | 79 |
| HVEM | Specific blockade of BTLA binding | None | Prevention from acute GVHD | 80 |
| PD-1H/ VISTA | PD-1H/VISTA agonist | None | Prevention from acute GVHD | 103 |
| Molecule . | Therapy . | Tumor . | Outcome . | Reference . |
|---|---|---|---|---|
| Autologous | ||||
| CTLA-4 | Anti–CTLA-4 + ova-DC vaccination | Thymoma | Improved tumor rejection, enhanced antigen-specific T-cell responses | 23 |
| CTLA-4 | Anti–CTLA-4; CTLA-4 deletional knockout | AML | Increased survival and improved tumor rejection | 22 |
| CTLA-4 | Anti–CTLA-4 | AML | Enhanced T-cell response, prolonged survival | 54 |
| PD-1 | Anti–PD-L1; PD-1 knockout | MM | Delayed tumor growth; complete tumor rejection in PD-1 knockout | 49 |
| PD-1 | HSCT + whole cell vaccination + anti–PD-L1 | MM | Increased survival | 52 |
| PD-1 | Anti–PD-L1; PD-1 knockout | AML | Enhanced T-cell response, improved tumor rejection, increased survival | 50 |
| PD-1/TIM-3 | Anti–PD-L1 and/or mTim-3 hFc | AML | Delayed tumor growth on monotherapy, improved tumor rejection on combined blockade | 93 |
| CD200 | Anti-CD200 | AML | Increased survival | 86 |
| CD200 | Anti-CD200 | B-CLL | Improved tumor rejection | 87 |
| CD200 | Anti-CD200 | B-cell lymphoma | Delayed tumor growth | 88 |
| Allogeneic | ||||
| CTLA-4 | Anti–CTLA-4 | AML | Enhanced T-cell response and GVHD early after BMT; enhanced tumor-specific T-cell response later after BMT with low GVHD | 28 |
| PD-1 | Anti–PD-L1 | Lymphoma | Enhanced T-cell response | 63 |
| PD-1 | Anti–PD-L1 | None | Enhanced alloreactive T-cell response, no GVHD | 64 |
| PD-1 | Anti–PD-L1; PD-1 knockout | CML | Increased survival | 65 |
| BTLA | BTLA agonist | B-cell lymphoma | Early after BMT: prevention of GVHD; later after BMT: no effect on GVHD; effective GVT response | 78 |
| BTLA | BTLA agonist | Mastocytoma/T-cell lymphoma | Inhibition of alloreactive T-cell response, prevention from GVHD | 79 |
| HVEM | Specific blockade of BTLA binding | None | Prevention from acute GVHD | 80 |
| PD-1H/ VISTA | PD-1H/VISTA agonist | None | Prevention from acute GVHD | 103 |
B-CLL indicates B-cell chronic lymphoid leukemia; and BMT, bone marrow transplantation.