New Drug Approach Could Roll Back Pancreatic Cancer Immunotherapy Resistance

New research by scientists from the Oregon Health & Science University and Johns Hopkins Kimmel Cancer Center has found a new approach that can make tumors resistant to immunotherapy vulnerable to the treatment.

For their study, the researchers evaluated the effectiveness and safety of the combination of 2 medications; entinostat, an epigenetic drug; and nivolumab, an immunotherapy medication. The drugs were administered to a group of twenty-seven patients with advanced pancreatic ductal adenocarcinoma. The patients had in the past undergone chemotherapy.

The immune activity in the microenvironment of patients with this common type of pancreatic cancer is suppressed, which allows the tumor to avoid attacks by the immune system.

The cancer attracts cells that suppress immune activity into the tumor, thereby limiting the access of T-cells into this environment. This increases resistance to immunotherapies that can successfully treat cancers like lung cancer and melanoma.

The team of researchers was led by Dr. Marinna Baretti and Dr. Nilofer Azad who co-leads the Cancer Genetics and Epigenetics Program. The researchers discovered that administering the drug combination resulted in tumor shrinkage, observing that the disease didn’t progress either for roughly 10 months.

In particular, they found that entinostat modified the tumor microenvironment by reducing the number of suppressive immune cells and growing proliferation and activation of T-cells in the region. This change in the environment allowed nivolumab to bring in more T-cells to eliminate tumor cells. Entinostat, a histone deacetylase inhibitor, is known to alter patterns of gene expression.

They also carried out lab analyzes of tissue and blood samples obtained from the patients, which helped demonstrate how the drugs performed on the microenvironment level.

The research is based on findings from two separate studies, one of which was led by Dr. Elizabeth Jaffee, Kimmel Cancer Center’s deputy director. The investigators discovered that entinostat could modify suppressive immune cell activity and bring in stronger T cells into the tumors.

A separate study also discovered that combining nivolumab and entinostat substantially enhanced survival in mice treated using both drugs, as compared to those that received only one of the drugs.

In their report, the researchers noted that their findings could help develop a road map that could be used in future trials for this pancreatic cancer and other cancers resistant to immunotherapies. They are now focused on understanding how this benefit can be expanded to help even more patients.

The study’s findings were reported in Nature Communications. The study was supported by the National Institutes of Health and the National Cancer Institute, among other institutions.

This additional information from this study about how to combat resistance to immunotherapy promises to expand the range of applicability of immunotherapies developed by companies like Scinai Immunotherapeutics Ltd. (NASDAQ: SCNI) targeting different malignancies.

NOTE TO INVESTORS: The latest news and updates relating to Scinai Immunotherapeutics Ltd. (NASDAQ: SCNI) are available in the company’s newsroom at https://ibn.fm/SCNI

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