A groundbreaking approach to cancer treatment, known as CAR-T cell therapy, has earned Dr. Michel Sadelain, director of the Columbia Initiative in Cell Engineering and Therapy (CICET), a prestigious BBVA Foundation Frontiers of Knowledge Prize in Biology and Biomedicine. The , announcement recognizes Dr. Sadelain’s pivotal role, shared with Dr. Carl June of the University of Pennsylvania, in revolutionizing how we fight cancer by harnessing the power of the body’s own immune system.
CAR-T cell therapy is a personalized treatment that involves modifying a patient’s T cells – a type of white blood cell crucial for immune function – to specifically recognize and destroy cancer cells. The process begins with isolating T cells from the patient’s blood. These cells are then genetically engineered to express a chimeric antigen receptor (CAR) on their surface. This synthetic receptor acts like a guided missile, enabling the T cells to identify and bind to a specific protein, or antigen, found on cancer cells. Once infused back into the patient, these “re-programmed” T cells actively seek out and eliminate cancer.
The concept of CAR-T cell therapy originated in the early 1990s, but early research by Dr. Sadelain and Dr. June focused on targeting CD19, a protein commonly found on leukemia and lymphoma cells. Initial laboratory and preclinical studies demonstrated promising results, paving the way for clinical trials. A major milestone was reached in with the FDA approval of the first CAR-T therapy for B-cell acute lymphoblastic leukemia (ALL) in patients whose cancer had not responded to conventional chemotherapy.
Since that initial approval, the field has rapidly expanded. Currently, seven CAR-T therapies are approved by the FDA for various blood cancers, including leukemia, lymphomas, and myelomas. These therapies have provided a new hope for patients who have exhausted other treatment options, with over 50,000 patients treated to date and many achieving remission. “It is now widely accepted that engineered immunity exemplified by CAR-T cells can succeed where no other treatment, chemotherapy, or bone marrow transplantation has before,” Dr. Sadelain stated.
The success of CAR-T cell therapy in blood cancers has spurred intense research into adapting the technology for solid tumors, which pose a greater challenge due to their complex microenvironment and ability to suppress immune responses. Dr. Sadelain and his team at CICET are actively working on strategies to overcome these hurdles. Their research extends beyond cancer, exploring the potential of CAR-T cell therapy to treat infectious diseases and autoimmune disorders.
Recent advancements have shown encouraging results in autoimmune conditions. Dr. Sadelain notes, “Recently, we have seen remarkable responses to CAR-T therapies in patients with autoimmune diseases such as lupus.” This suggests that CAR-T cell therapy’s ability to precisely target and eliminate specific immune cells could offer a novel approach to managing autoimmune diseases, where the immune system mistakenly attacks the body’s own tissues.
Dr. Sadelain expresses optimism about the future of CAR-T cell therapy. “I believe there’s every reason to be optimistic that in the next few years, certainly the next decade, we will have effective CAR-T cell therapies for brain tumors and other solid cancers,” he says. The development of CAR-T therapies for solid tumors requires addressing challenges such as identifying appropriate target antigens, enhancing T cell penetration into tumors, and overcoming immunosuppressive mechanisms within the tumor microenvironment.
Dr. Sadelain’s career has been marked by significant contributions to the field of genetic engineering and cell therapy. Prior to his role at Columbia University, he served as the Steve and Barbara Friedman Chair, founding director of the Center for Cell Engineering, and head of the Gene Transfer and Gene Expression Laboratory at Memorial Sloan Kettering Cancer Center. He is also recognized for his pioneering work in lentiviral vectors for treating severe hemoglobinopathies like β-thalassemia and sickle cell disease.
His dedication to advancing the field has been recognized with numerous awards, including the Passano Award, the Jacob and Louise Gabbay Award in Biotechnology and Medicine, the INSERM International Prize, the Leopold Griffuel Award, the ASGCT Outstanding Achievement Award, and more recently, the AACR Elected Fellow, the / Meyenburg Prize, the Breakthrough Prize in Life Sciences, the Canada Gairdner International Award, the Warren Alpert Foundation Prize, the King Faisal Prize, the Merkin Prize, and the Broermann Medical Innovation Award. The BBVA Foundation Frontiers of Knowledge Prize adds to this impressive list, solidifying Dr. Sadelain’s legacy as a leader in the field of cancer immunotherapy.
The ongoing research at CICET and other institutions worldwide promises to further refine CAR-T cell therapy, making it more effective, safer, and accessible to a wider range of patients battling cancer and other challenging diseases.
