Outcome of interference with human coinhibitory molecules
| Molecule . | Therapy . | Tumor . | Outcome . | Reference . |
|---|---|---|---|---|
| CTLA-4 | Ipilimumab, in vivo | NHL | Two of 4 tumor regression, no increase in vaccine-specific T-cell responses, reduction in TREG number early after treatment; toxicity: mainly grade 1 or 2, 1 times grade 3 | 24 |
| CTLA-4 | Ipilimumab, in vivo | Relapsed/refractory B-cell NHL | Two of 18 clinical response, 5 of 16 enhanced T-cell response to recall Ag; toxicity: mainly grade 1 or 2, 6 of 18 grade 3 | 25 |
| CTLA-4 | Ipilimumab after alloSCT, in vivo | AML, CML, CLL, HL, NHL, MM | Three of 29 clinical response; toxicity: no induction of GVHD, 4 of 29 organ-specific immune adverse events | 29 |
| CTLA-4 | Anti–CTLA-4, ex vivo | HL | Abrogated TREG suppression | 17 |
| CTLA-4 | Anti–CTLA-4, ex vivo | CLL | Enhanced tumor-specific T-cell response | 109 |
| PD-1 | BMS-936,558, ex vivo | ALL, AML, CML, NHL, MM | Enhanced alloreactive T-cell response | 20 |
| PD-1 | Anti–PD-L1, ex vivo | NHL | Enhanced T-cell response | 52 |
| PD-1 | Anti–PD-L1 and anti–PD-L2, ex vivo | HL | Restored T-cell response | 53 |
| PD-1 | Anti–PD-L1, ex vivo | HCV lymphoma | Abrogated TREG suppression, reduction in Treg number | 55 |
| PD-1 | CT-011, in vivo | AML, CLL, HL, NHL, MDS, MM | Six of 17 clinical response, 1 complete remission, no toxicity | 57 |
| PD-1 | CT-011 with or without lenalidomide, ex vivo | MM | Enhanced NK cytotoxicity, additive effect of lenalidomide | 58 |
| PD-1 | CT-011 + tumor/DC vaccination, ex vivo | MM | Reduction in TREG number, enhanced T-cell response | 59 |
| PD-1 | DC vaccination with PD-L silencing, ex vivo | AML, CML | Enhanced alloreactive T-cell response | 105 |
| BTLA | Anti-BTLA, ex vivo | ALL, AML, CML, NHL, MM | Enhanced alloreactive T-cell response | 67 |
| CD200 | Anti-CD200, ex vivo | AML | Enhanced NK cytotoxicity | 84 |
| CD200 | Anti-CD200, ex vivo | CLL | Enhanced antigen-specific T-cell responses, reduction in Treg number | 85 |
| Molecule . | Therapy . | Tumor . | Outcome . | Reference . |
|---|---|---|---|---|
| CTLA-4 | Ipilimumab, in vivo | NHL | Two of 4 tumor regression, no increase in vaccine-specific T-cell responses, reduction in TREG number early after treatment; toxicity: mainly grade 1 or 2, 1 times grade 3 | 24 |
| CTLA-4 | Ipilimumab, in vivo | Relapsed/refractory B-cell NHL | Two of 18 clinical response, 5 of 16 enhanced T-cell response to recall Ag; toxicity: mainly grade 1 or 2, 6 of 18 grade 3 | 25 |
| CTLA-4 | Ipilimumab after alloSCT, in vivo | AML, CML, CLL, HL, NHL, MM | Three of 29 clinical response; toxicity: no induction of GVHD, 4 of 29 organ-specific immune adverse events | 29 |
| CTLA-4 | Anti–CTLA-4, ex vivo | HL | Abrogated TREG suppression | 17 |
| CTLA-4 | Anti–CTLA-4, ex vivo | CLL | Enhanced tumor-specific T-cell response | 109 |
| PD-1 | BMS-936,558, ex vivo | ALL, AML, CML, NHL, MM | Enhanced alloreactive T-cell response | 20 |
| PD-1 | Anti–PD-L1, ex vivo | NHL | Enhanced T-cell response | 52 |
| PD-1 | Anti–PD-L1 and anti–PD-L2, ex vivo | HL | Restored T-cell response | 53 |
| PD-1 | Anti–PD-L1, ex vivo | HCV lymphoma | Abrogated TREG suppression, reduction in Treg number | 55 |
| PD-1 | CT-011, in vivo | AML, CLL, HL, NHL, MDS, MM | Six of 17 clinical response, 1 complete remission, no toxicity | 57 |
| PD-1 | CT-011 with or without lenalidomide, ex vivo | MM | Enhanced NK cytotoxicity, additive effect of lenalidomide | 58 |
| PD-1 | CT-011 + tumor/DC vaccination, ex vivo | MM | Reduction in TREG number, enhanced T-cell response | 59 |
| PD-1 | DC vaccination with PD-L silencing, ex vivo | AML, CML | Enhanced alloreactive T-cell response | 105 |
| BTLA | Anti-BTLA, ex vivo | ALL, AML, CML, NHL, MM | Enhanced alloreactive T-cell response | 67 |
| CD200 | Anti-CD200, ex vivo | AML | Enhanced NK cytotoxicity | 84 |
| CD200 | Anti-CD200, ex vivo | CLL | Enhanced antigen-specific T-cell responses, reduction in Treg number | 85 |
ALL indicates acute lymphoid leukemia; CLL, chronic lymphoid leukemia; NHL, non-Hodgkin lymphoma; MDS, myelodysplastic syndrome; HCV, hepatitis C virus; and GI, gastrointestinal tract.