A new class of therapies called BET inhibitors bolstered anti-tumor immunity in mouse models of lymphoma, offering a promising new approach to enhancing blood cancer therapies, according to a study.
Researchers obtained the result by switching off the expression of the PD-L1 protein, which tumor cells often use to evade immune surveillance.
The study, “BET-Bromodomain Inhibitors Engage the Host Immune System and Regulate Expression of the Immune Checkpoint Ligand PD-L1,” was published in Cell Reports.
BET inhibitors prevent tumor cells from expressing cancer-causing genes. This prevents cell proliferation and triggers cell death.
Researchers at Monash University and the Peter MacCallum Cancer Center discovered that a normal immune system makes BET inhibitor treatment more effective. In fact, when immune-deficient mice with lymphoma were treated with the inhibitors, they died sooner than mice with functioning immune systems.
The findings suggested that BET inhibitors could be working to bolster immune system activity.
One thing researchers wanted to know was what genes the BET inhibitors affected. They discovered that the drugs could stop tumor cells from producing the PD-L1 protein.
The protein works as a flag in cancer cells, telling immune cells to leave the cancer cells alone. By preventing the production of the protein, BET inhibitors made the tumor cells more susceptible to an immune system response.
Drugs such as Keytruda (pembrolizumab) and Opdivo (nivolumab) have proven effective in blocking the PD-1/PD-L1 pathway in a number of tumor types.
Combining BET inhibitors with an antibody targeting the PD-1 protein provided better results than any therapy alone in lymphoma mouse models, the research team found.
International clinical trials are under way to test BET inhibitors as a treatment for blood cancers. The Monash researchers’ findings prompted them to start a new trial (NCT02684617) assessing a drug called Dinaciclib in combination with the anti-PD-1 Keytruda as a treatment for relapsed lymphoma, chronic lymphocytic leukemia, and myeloma.
The findings are likely to lead to further clinical trials assessing a combination of BET inhibitors and anti-PD-1 therapies, according to a press release.
