Table 1:
Therapies evaluating various immune targets in MDS.
| Class | Therapy | Target | Mechanism | Clinical Trial | Status |
|---|---|---|---|---|---|
| TLR signaling | OPN-305 | TLR2 | Humanized anti-TLR2 mAB | NCT02363491: second-line treatment for lower risk MDS | Phase I/II, recruiting |
| CX-01 | TLR4 | Heparin-derived polysaccharide disrupts interaction between TLR4 and HMGB1 | NCT02995655: combination therapy with azacitidine in R/R MDS and AML | Phase I, recruiting | |
| Cytokine inhibitors | Etanercept | TNFα | Soluble TNFa receptor | NCT00118287: combination azacitidine and Etanercept in MDS | Phase I/II, completed |
| Siltuximab | IL-6 | Chimeric monoclonal antibody to IL-6 | NCT01513317: siltuximab vs. placebo with best supportive care in anemic patients with IPSS low or intermediate-1 risk MDS | Phase II, terminated | |
| Luspatercept | TGFβ | ||||
| p38 inhibitor | Talmapimod (SCIO-469) | p38 | Inhibitor of p38α | NCT00113893: open label study for any patient with MDS | Phase II, completed |
| ARRY-614 | p38/Tie2 | Inhibitor of p38 and Tie2 | NCT00916227: ARRY-614 in patients with IPSS low or intermediate-1 risk MDS | Phase I, completed | |
| Checkpoint inhibitor | Pembrolizumab (MK-3475) | PD-1 | Monoclonal antibody to PD-1 | NCT01953692: Pembrolizumab in patients with blood cancers | Phase Ib, active not recruiting |
| Nivolumab | PD-1 | Monoclonal antibody to PD-1 | NCT02464657: safety and efficacy of nivolumab in combination with idarubicin and cytarabine in MDS and AML | Phase I/II, recruiting | |
| Nivolumab | PD-1 | Monoclonal antibody to PD-1 | NCT 03417154: nivolumab and cyclophosphamide in R/R AML and high risk MDS | Phase II, not yet recruiting | |
| Ipiliumab | CTLA-4 | Monoclonal antibody to CTLA-4 | NCT02530463: nivolumab and/or ipililumab, with or without azacitidine in MDS | Phase II, recruiting | |
| Trispecific Killer Cell Engager | CD16/IL-15/CD33 TRiKE | CD16/CD33 | anti-CD16 single chain variable fragment (scFv) to engage NK cells and anti-CD33 scFv with a modified IL-15 linker | NCT03214666: CD16/IL-15/CD33 TRiKE for CD33 hematological malignancies | Phase I/II, not yet recruiting |
| Dual Affinity Retargeting molecule | Flotetuzumab (MGD006) | CD123/CD3 | DART recognizing CD123 and CD3 | NCT02152956: safety of MGD006 in R/R AML or IPSS intermediate-2 or high risk MDS | Phase I, recruiting |
| Monoclonal Antibody | BI 836858 | CD33 | Monoclonal antibody to CD33 | NCT02240706: BI836858 vs. best supportive care in patients with IPSS low or intermediate-1 risk MDS | Phase I/II, recruiting |
| Vaccine therapies | PR1 Leukemia Peptide Vaccine | Stimulates host’s immune system to mount a cytotoxic T lymphocyte response to tumor cells | NCT00004918: Vaccine Immune Adjuvant in Chronic Myeloid Leukemia (CML), AML or MDS | Phase I/II, completed | |
| DEC-205/NY-ESO-1 Fusion Protein CDX-1401 | Stimulates host’s immune system to mount a cytotoxic T lymphocyte response to tumor cells | NCT03358719: DEC-205/NY-ESO-1 Fusion Protein CDX-1401, Poly ICLC, Decitabine, and Nivolumab in Treating Patients With MDS or AML | Phase I, not yet recruiting | ||
| NK cellular therapy | Lirilumab | KIR2DL½L3 | Monoclonal antibody to KIR2DL½L3 | NCT 02599649: nivolumab and/or lirilumab, with or without azacitidine in MDS | Phase II, recruiting |
| Activated NK cells | - | Expansion of NK cells ex vivo in presence of irradiated K562 cell line | NCT02123836: NK cell therapy in AML and MDS | Phase I, recruiting | |
| Activated NK cells | - | Donor NK cell transfusion | NCT01898793: Cytokine-induced Memory-like NK Cells in Patients With AML or MDS | Phase I/II, recruiting | |
| Activated NK cells | Donor NK cell transfusion | NCT02890758: Universal Donor NK Cell Therapy in Combination with ALT803 | Phase I, recruiting | ||
| CAR T cell targeting NKG2D-ligand | CART T cells targeting NKG2D-ligands on myeloid cells | NCT02203825: Safety Study of Chimeric Antigen Receptor Modified T-cells Targeting NKG2D-Ligands in MDS/AML/MM | Phase I, not yet recruiting |