Otsuka Pharmaceutical's (TYO:4578) Dacogen (decitabine) may expand the range of tumors that can be targeted with anti-NY-ESO-1 immunotherapies given its ability to induce NY-ESO-1 tumor antigen expression, experts said.
Dacogen, a hypomethylating agent (HMA) normally used to treat certain blood cancers, can force certain tumors that do not normally express NY-ESO-1 to express the antigen, such as acute myeloid leukemia (AML), myelodysplastic syndrome (MDS) and glioblastoma (GBM), several experts noted. However, whether the approach might work depends on whether the NY-ESO-1 promoter is methylated in a particular cancer versus the cancer simply not expressing the gene, an expert added. Others were skeptical of what they consider to be a hypothesis-driven approach, while expressing concerns that using nontargeted drugs like Dacogen to unmask NY-ESO-1 may unintentionally concurrently unmask other antigens, with unknown consequences.
The success of NY-ESO-1-targeting immunotherapies will likely be underscored by checkpoint inhibitor/vaccine combinations as well as T-cell receptor (TCR) approaches, this news service previously reported. While Adaptimmune (NASDAQ:ADAP) and Immune Design (NASDAQ:IMDZ) are using a modified TCR approach with a Phase I/II NY-ESO TCR, and Phase I LV305 with CMB305, respectively, for multiple cancers, Celldex (NASDAQ:CLDX) is exploring a vaccine approach in different cancers with the Phase II CDX-1401, an NY-ESO-1-targeting vaccine. Early trials at academic centers like Memorial Sloan Kettering, New York and Roswell Park Cancer Institute are also underway.