CAR-T Therapy Challenges: The ANXA1 Connection

Multiple myeloma (MM) is a type of cancer that affects plasma cells. It can be treated with CAR-T cell therapy, which uses engineered T cells to target and kill cancer cells. However, relapse can happen. The relapse can occur even after a long period of remission. This is a big problem. It can happen because the cancer cells change and become resistant to the treatment. This is what happened to a patient who had a relapse after 12 months of remission. The patient's bone marrow showed that the CAR-T cells were exhausted and not multiplying as they should. The cancer cells that came back were different. They did not have the BCMA protein that the CAR-T cells were designed to target. This means the CAR-T cells could not recognize and attack these cancer cells. The cancer cells also had high levels of a protein called ANXA1. This protein is known to be a bad sign for MM patients. The cancer cells with high ANXA1 levels were found in patients who had not even received CAR-T therapy. This suggests that ANXA1 might play a role in making cancer cells resistant to treatment. Lab tests showed that high ANXA1 levels helped the cancer cells grow and made the CAR-T cells less effective. When ANXA1 was blocked, the cancer cells grew less. This was also seen in mouse models, where blocking ANXA1 helped reduce the number of cancer cells that escaped the CAR-T cell attack. So, ANXA1 could be a new target for treating MM, especially for patients who relapse after CAR-T therapy. By targeting ANXA1, doctors might be able to make CAR-T therapy more effective. This could help more patients achieve long-term remission. However, more research is needed to fully understand how ANXA1 works and how best to target it. It's important to note that cancer is complex. Many factors can contribute to relapse. Understanding these factors can help improve treatments. This study provides new insights into what might be happening when MM relapses after CAR-T therapy. It also suggests a potential new target for treatment.