Chimeric Antigen Receptor T-cell Therapy


Chimeric Antigen Receptor T-cell Therapy


Gergana Kostova, Aleksandra Sokolova
Faculty of Chemistry and Pharmacy, University of Sofia ‘‘St. Kliment Ohridski”


Cancer treatment has undergone massive changes with the introduction of new modalities in the recent past that have helped to improve outcomes of treatment. In the past, surgery, chemotherapy, and radiation therapy were the only known modalities used for cancer treatment. Later, monoclonal antibody therapies were introduced which utilized targeting specific molecular changes seen in cancer cells. Most recently, immunotherapy has emerged as one of the most promising modalities in cancer treatment. It involves strengthening of the patient’s immune system to facilitate attack to the malignant cells. Adoptive cell transfer (ACT) is one of the immunotherapy approaches which consists of collecting patient’s immune cells and modifying them to treat cancer. There are many types of the ACT, but only CAR T-cell therapy has gained a lot of popularity. CAR T-cells have been dubbed a “Living Drug” as they function to eliminate malignant cells in the body. T cells are the primary cells used in the development of CAR T-cell therapy. Blood is drawn from patients and T cells are separated from other cells. These T cells are then exposed to disarmed viruses which enable them to develop receptor antigens specific for the virus called chimeric antigen receptors. These receptors are responsible for recognizing particular antigens in tumor cells and destroying them after the T-cells are infused back into the circulation. Some of these tumor-specific antigens targeted include CD 19 in B cells and CD 22 protein. Most of the CAR T-cell therapy studies are in Acute Lymphoblastic Leukemia in children who have relapsed disease. Other studies have been conducted in patients with advanced lymphomas. The most common side effect of CAR T-cell therapy is the cytokine release syndrome. Others include B cell aphasia, cerebral edema, neurotoxicities among others. CAR T-cell therapy has shown initial signs of success in hematological malignancies such as leukemia in children. However, efforts to find specific antigens in solid tumors have proved to be futile.