HDAC Inhibitor Improves Immunotherapy in Lung Cancer

Only 20% of lung cancer patients show a response to current immunotherapeutic antibodies.

A histone deacetylase (HDAC) inhibitor used in combination with a PD-1 targeting antibody can enhance immunotherapy for lung cancer, a recent study indicates.

The study, published in Clinical Cancer Research, analyzed 97 FDA agents that could increase the expression of chemokines and stimulate T cells in vitro. The HDAC inhibitor romidepsin was the only 1 with the ability to stimulate T cell tumor activity and infiltration.

While using a mouse model, researchers were able to demonstrate that romidepsin significantly decreased lung tumor growth.

The results of the study suggest that HDAC inhibitors could work in conjunction with other immune-stimulating agents to enhance an immune response against tumors.

Data results confirmed that romidepsin combined with an antibody that targets PD-1 showed greater anti-tumor activity compared with using the agents alone. Additionally, the combination increased T cell levels and activity inside the tumor.

“These results suggest that combination of HDAC inhibitors with PD-1 blockade represents a promising strategy for lung cancer treatment,” said Amer Beg, PhD, senior member of the Immunology Program at Moffitt.

Although there are other immunotherapeutic antibodies approved for the treatment of advanced stage lung cancer and melanoma, only 20% of lung cancer patients show a response.

Currently, researchers are recruiting patients to participate in a clinical trial to test the combination of an HDAC inhibitor and a PD-1 inhibitor in stage 4 non-small cell lung cancer.