Combination Therapy Shows Promise in Lung Cancer Patients
HDAC inhibitors in combination with immune-stimulating agents improve tumor response.
With only 20% of lung cancer patients responding to new immunotherapeutic antibodies, Moffitt Cancer Center researchers sought to improve this statistic with a combination therapy that makes T cells more active within a tumor.
Some of the current lung cancer therapies, such as PD-1-targeted antibodies, do not work in some patients. In this case, low levels of immune T cells are associated with a poor response to PD-1-targeted treatments.
The researchers believe that increasing the activity of T cells within the tumor itself could increase the efficacy of PD-1- targeted treatments, thus helping the therapy achieve a higher success rate. Researchers hope to accomplish this goal with small molecule drugs that increase the activity of T cells.
These molecules are called chemokines, which are chemical messengers that “stimulate T cell tumor infiltration and activity.” The introduction of these chemokines are the critical part of this research, since they could potentially decrease tumor growth.
The researchers found that the histone deacetylase (HDAC) inhibitor romidepsin was the only molecule that could be manipulated in vitro. Romidespin and other HDAC inhibitors can treat hematological malignancies, but have not been effective treating solid tumors on its own.
In the current study, it was found that mice experienced a decrease in lung tumor growth. This is likely because romidepsin is able to “induce chemokines and T cell filtration into cells.”
As a result of the study, the researchers believe that introducing an HDAC inhibitor may be able to achieve the same result in humans.
The study further showed that romidepsin combined with PD-1 targeting antibody showed greater anti-tumor activity than either agent individually. This treatment also increases T cell levels within the tumor and T cell activity.
By combining 2 different anti-bodies, patients who would normally be unresponsive to 1 treatment are able to reap the benefits of both.
A combination therapy is currently being evaluated in clinical trials for Stage IV lung cancer patients. This therapy will include an HDAC inhibitor, as well as a PD-1 inhibitor. "These results suggest that combination of HDAC inhibitors with PD-1 blockade represents a promising strategy for lung cancer treatment," Amer Beg, PhD, a senior member of the Immunology Program at Moffitt, said in a press release.