CAR T-cell therapy is a personalized cancer treatment that harnesses the body’s immune system. This method involves modifying a patient’s immune cells to specifically target and eliminate cancer cells. It offers a new approach in oncology, particularly for patients with certain blood cancers who have limited treatment options. The therapy provides new avenues for durable responses in challenging cases.
How CAR T-Cell Therapy Works
The process of CAR T-cell therapy begins with the collection of a patient’s T cells, a type of white blood cell, through a procedure called apheresis. During apheresis, blood is drawn from the patient, and T cells are separated before the remaining blood is returned to the body. These collected T cells are then sent to a specialized laboratory for genetic modification.
In the laboratory, T cells are engineered to produce chimeric antigen receptors (CARs) on their surface. This involves introducing a new gene that enables them to recognize a specific antigen found on cancer cells. The CAR allows the modified T cells to precisely identify and bind to cancerous cells.
Once modified, these CAR T cells are expanded in the lab, multiplying until there are sufficient numbers to effectively combat the cancer. Following this expansion, the CAR T cells are infused back into the patient’s bloodstream, similar to a blood transfusion. Upon reinfusion, these re-engineered cells circulate throughout the body, actively seeking out and destroying cancer cells that display the targeted antigen. This targeted attack is initiated by the binding of the CAR to the tumor antigen, which then activates the T cell to release cytotoxic molecules like perforin and granzymes, leading to cancer cell destruction.
Cancers Treated with CAR T-Cell Therapy
CAR T-cell therapy treats specific types of blood cancers, particularly in patients who have not responded to other treatments or whose cancer has returned. The U.S. Food and Drug Administration (FDA) has approved several CAR T-cell therapies for various hematologic malignancies.
One early approval was for B-cell precursor acute lymphoblastic leukemia (ALL) in children and young adults. This therapy is used when leukemia has resisted prior treatments or has relapsed. For adult patients, CAR T-cell therapies are approved for various forms of B-cell non-Hodgkin lymphoma, including diffuse large B-cell lymphoma (DLBCL), primary mediastinal large B-cell lymphoma, and mantle cell lymphoma. These therapies are for patients whose lymphoma has relapsed or is refractory to at least two other lines of therapy.
Follicular lymphoma that has relapsed or is refractory after two prior therapies also has an approved CAR T-cell option. Multiple myeloma, an uncommon blood cancer affecting the bone marrow, has also seen the approval of CAR T-cell therapies for adult patients who have progressed after multiple prior treatments.
Transformative Patient Outcomes
CAR T-cell therapy has led to positive outcomes for patients battling aggressive blood cancers, often offering a chance at durable remission even after other treatments have failed. For many individuals, this therapy has translated into long-term survival, previously unachievable with conventional approaches. Some patients have experienced remission lasting for more than a decade.
The therapy’s impact extends beyond just survival rates; it also significantly improves the quality of life for many recipients. While there can be initial side effects and a period of recovery, studies indicate that most patients experience a substantial improvement in their reported well-being within six months post-infusion. This improvement includes a reduction in physical symptom burden and anxiety, allowing patients to return to more normal daily activities.
For patients with advanced lymphomas, the treatment has shown positive results, with some trials showing that more than 30% of participants with large cell lymphoma were alive without any evidence of cancer five years after treatment. In cases of advanced follicular lymphoma, one CAR T-cell therapy eliminated the cancer in nearly 80% of patients, with many remaining disease-free after three years. These outcomes highlight the therapy’s ability to provide a sustained, deep response.
Expanding Reach of CAR T-Cell Therapy
The success of CAR T-cell therapy in blood cancers has spurred extensive research into its application for a broader range of malignancies, including solid tumors. While translating this success to solid tumors presents unique challenges, such as the hostile tumor microenvironment and tumor heterogeneity, promising outcomes are emerging from ongoing clinical trials. Efforts are underway to engineer CAR T cells that can better infiltrate and persist within solid tumor sites and overcome immunosuppressive factors.
Researchers are exploring various strategies, including enhanced delivery methods like locoregional administration for brain tumors, to increase CAR T-cell concentration at the tumor site and reduce systemic side effects. New CAR designs are being developed to target different antigens on solid tumor cells, aiming to improve specificity and efficacy. Combining CAR T-cell therapy with other treatments, such as chemotherapy or immune checkpoint inhibitors, is also being investigated to enhance its activity and persistence.