Reprogramming the immune system for cancer: The promise of CAR T-cell therapy and beyond

Advancements in early detection, precise diagnostic tools, and potent treatments, including immunotherapy and targeted therapies, have led to decreased cancer mortality rates and improved patient outcomes. Immunotherapy, including checkpoint inhibitors, CAR-T cell therapy, and cancer vaccines, uses the body's immune system to recognize and destroy cancer cells, particularly in difficult-to-treat cancers like melanoma and lung cancer. Targeted therapies target specific molecular targets associated with cancer growth and progression. Recent years have seen a proliferation of cancer treatments approved by the Food and Drug Administration (FDA) that draw on a lengthy history of therapeutic uses for redirected T cells and Chimeric Antigen Receptors (CARs). Chimeric antigen receptor (CAR) T-cell therapy has emerged as a cutting-edge and highly promising approach for cancer treatment. This therapy entails the genetic engineering of T cells extracted from the patient's blood, followed by their re-infusion into the patient. While CAR T-cell therapy has demonstrated exceptional success in treating hematologic cancers such as leukemia and lymphoma, its application to solid tumors has presented considerable obstacles. The tumor microenvironment (TME) in solid tumors is frequently hostile to immune cells, with physical obstacles, immunosuppressive cells, and inhibitory cytokines limiting the efficiency of CAR T-cells. Recent advancements aim to overcome challenges associated with CART therapy, including efficacy in solid tumors with few challenges. Strategies under investigation include modifying CART cells to improve their tumor infiltration, persistence, and resistance to immunosuppressive tumor microenvironments. The current study focuses on the development, challenges, and potential future paths of CAR T-cell therapy.