Table 3.
Epigenetic- and immunotherapy-based attempts to target GSCs.
| Epigenetic inhibitors | ||||||||
|---|---|---|---|---|---|---|---|---|
| Drug | Target | Stage | Trial Phase | Context | Other treatments | Outcome | Ref(s) | NCT # |
| Decitabine | DNMTs | Pre-clinical | NA | Murine GSCs | NA | Increased T cell-mediated killing of GSCs | (46) | NA |
| Decitabine | DNMTs | Pre-clinical | NA | Patient-derived primary GBM cell lines | NA | Increased antigen-specific T cell-mediated glioma cytotoxicity | (185) | NA |
| JQ1 | Pan-BET | Pre-clinical | NA | Human GBM neurospheres | NA | Reduced expression of immunosuppressive transcriptome in GSCs; Reduced immunosuppressive effect on T cells & M2 macrophage polarization | (17) | NA |
| PCI-34051 | HDAC8 | Pre-clinical | NA | Murine glioma mouse model | NA | Prolonged survival; Reduced invasion of anti-inflammatory microglia; Increased NK cell-mediated glioma cytotoxicity | (104) | NA |
| Vorinostat | HDACs | Pre-clinical | NA | Murine glioma mouse model | GSC lysate vaccine | Prolonged survival and increased T cell tumor infiltration | (44) | NA |
| Vorinostat | HDACs | Clinical | I/II | Newly diagnosed GBM | SOC | Did not meet primary efficacy endpoint (OS = 15mo) | (186) | NCT00731731 |
| Vorinostat | HDACs | Clinical | II | Recurrent GBM | Prior SOC | Modest effects; Met primary efficacy endpoint (PFS = 6mo) | (187) | NCT00238303 |
| Vorinostat | HDACs | Clinical | I/II | Recurrent GBM | Bevacizumab, TMZ | Met primary endpoint (PFS = 6mo); Improvement in PFS not statistically significant | (188) | NCT00939991 |
| Vorinostat | HDACs | Clinical | II | Recurrent GBM | Bevacizumab | No significant improvement in PFS or OS | (189) | NCT01266031 |
| Romidepsin | HDACs | Clinical | I/II | Recurrent glioma | Prior SOC | Did not meet primary efficacy endpoint (PFS = 6mo) | (190) | NCT00085540 |
| Panobinostat | HDACs | Clinical | II | Recurrent GBM | Bevacizumab | No significant improvement in PFS | (191) | NCT00859222 |
| Epigenetic inhibitors plus immunotherapy | ||||||||
| JQ1 +CAR-T cells | Pan-BET, EGFR | Pre-clinical | NA | Human GBM mouse model | NA | Prolonged survival | (192) | NA |
| Azacytidine + Nivolumab | DNMTs, PD1 | Clinical | I/II | IDH-mutant gliomas | SOC | Completed - No Results | NA | NCT03684811 |
| Vorinostat + Pembrolizumab | HDACs, PD1 | Clinical | I | Newly diagnosed GBM | SOC | Active | NA | NCT03426891 |
SOC, standard-of-care treatment (surgery followed by TMZ & radiation); OS, overall survival; PFS, progression-free survival.