Researchers Identify Key Source of T-Cell “Exhaustion”–Discovery May Open Way to Drugs That Can Prevent T-Cell Therapies from Losing Their Potency Over Time

Dr. Cigall Kadoch

Custom-made to attack cancer cells, CAR T-cell therapies have opened a new era in the treatment of human cancers, particularly, in hematologic malignancies. All too often, however, the CAR T cells display a frustrating trait inherited from the body's own immune system cells: a drastic loss of cancer-fighting fervor known as "exhaustion.” Exhaustion is not only seen in cancer-fighting T cells but is also frequent in the setting of viral infections, such as human immunodeficiency virus (HIV), hepatitis B/C viruses (HBV, HCV) and COVID-19 (SARS-CoV-2). The lapse into listlessness has diminished the effectiveness of CAR T-cell therapies in some patients and prompted scientists to try to find its source.  In a new study, scientists at Dana-Farber Cancer Institute and NYU Grossman School of Medicine show the commanding role of a specialized group of proteins in the nuclei of our cells, called mSWI/SNF (or BAF) complexes, both in activating T cells to attack cancer and triggering exhaustion.

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