Table 1.
In vivo pre-clinical tests showing promising molecules against multiple myeloma (MM) bone marrow (BM) milieu to overcome immunosuppression.
| Molecular Target |
In Vivo Pre-Clinical Studies | Reference |
|---|---|---|
| IL-18 in MDSCs | Long-term blockade of IL-18 delayed MM progression. Additionally, the combination of IL-18 mAb+Bortezomib significantly prolonged survival in MM models originally established as Bortezomib resistant. | Nakamura et al., 2018 [117] |
| piRNA-823 | Silencing piRNA-823 in MM reduced the stemness of myeloma stem cells maintained by PMN-MDSCs, decreased tumour burden and angiogenesis in vivo. | Ai et al., 2019 [118] |
| DCs vaccination + Lenalidomide + anti-PD-1 mAb | This triple combination synergistically induced a stronger anti-tumour immune response by inhibiting MM growth in a murine model. | Vo et al., 2018 [119] |
| TRL9 agonist C792 | C792 recovers pDCs ability to stimulate T cells and inhibits myeloma cell growth. Importantly, this cytotoxic activity enhances bortezomib, lenalidomide, SAHA or melphalan. | Ray et al., 2014 [120] |
| Clodronate-liposomes | Depletion of CD169+ bone marrow–resident macrophages in vivo abrogates myeloma growth. | Opperman et al., 2019 [121] |
| CD40 mAb + CpG (TLR9) | Macrophage-activating immunotherapy using CD40 plus CpG promoted anti-tumor effect in a RR MM murine model. This effect was increased when Tpl2 kinase was also inhibited showing an increase in both progression-free survival and overall survival. | Jensen et al., 2015 [122] |
| Anti-PD-1 mAb | Treatment with anti-PD-1 ex vivo reinvigorated T cells that expressed exhausted and senescence markers to produce effector cytokines. | Chung et al., 2016 [73] |
| Anti-TIGIT mAb expressed in T cells | In Vk*MYC TIGIT-null mice, myeloma growth was delayed and in wild type mice tumor burden was reduced with anti-TIGIT treatment. | Guillerey et al., 2018 [76] |
| CS1-NKG2D bi-specific antibody in NK cells | Anti-TIGIT treatment was able to improve disease control rates in a murine model of MM relapse after stem cell transplant. Prolonged survival in a humanized MM model. |
Minnie et al., 2018 [21] Chang et al., 2018 [123] |