Researchers improve CAR-T therapy for B-ALL cancers

Researchers have developed a new strategy to improve CAR-T therapy for patients with B-cell Acute Lymphoblastic Leukemia (B-ALL). This aggressive type of blood cancer is particularly common in children but can affect anyone. Although CAR-T cell therapy has helped many patients, more than half still experience a relapse. A significant challenge with CAR-T therapy is understanding why the modified T-cells sometimes do not fight off the cancer effectively. Researchers found that B-ALL tumors can exploit the immune system's natural defenses to avoid being destroyed by these engineered cells. Tumors can take advantage of immune checkpoints, which typically signal immune cells to stop attacking after a threat is cleared. In CAR-T therapy, T-lymphocytes are taken from a patient’s blood, modified in a lab, and then reintroduced to target cancer cells. However, some leukemia cells have high levels of galectin-9, which interacts with TIM-3 on CAR-T cells. This interaction may "turn off" the CAR-T cells, allowing the cancer to survive. To counter this, scientists created a TIM-3 decoy, which blocks the interaction between galectin-9 and TIM-3. This decoy aims to keep the CAR-T cells active against the leukemia. Preliminary tests on genetically modified mice showed great promise. The CAR-T cells that produced the TIM-3 decoy were more effective at combating leukemia and lasted longer in the body. While this research is still in the early stages, it represents a significant step toward better treatments for B-ALL. The goal is to make CAR-T therapy more effective and reduce the rates of relapse. Researchers hope this new approach can eventually lead to “armored CAR-T cells” that may also help treat solid tumors. The study involved teams from various institutions, including the Josep Carreras Leukaemia Research Institute and other European organizations.