Scientists have found the source of T cell exhaustion, a problem that reduces the effectiveness of CAR T-cell therapy, a treatment used to fight cancer. CAR T-cell therapy uses a patient's immune system T cells, modifies them to attack cancer cells, and then injects them back into the patient. However, these T cells often become exhausted and stop fighting cancer.
Researchers from Dana-Farber Cancer Institute and NYU Grossman School of Medicine have discovered that mSWI/SNF protein complexes play a crucial role in both activating T cells and causing exhaustion. This finding, published in the journal Molecular Cell, suggests that targeting these complexes could reduce exhaustion and improve the ability of CAR T cells to fight cancer.
The scientists found that the location of mSWI/SNF complexes on T cell DNA changes depending on certain proteins called transcription factors. By inhibiting specific genes related to these complexes, the T cells were able to continue fighting cancer without becoming exhausted. The researchers also used new inhibitors to reverse the exhaustion process, making the T cells more active and similar to memory-like T cells.
This discovery is particularly significant as the first inhibitors targeting mSWI/SNF complexes are currently being tested in phase 1 clinical trials for cancer treatment. Animal experiments have shown promising results, with reduced tumor growth when treated with CAR T cells exposed to mSWI/SNF inhibitors.
This groundbreaking research offers new hope for patients undergoing CAR T-cell therapy. By understanding the underlying cause of T cell exhaustion, scientists can develop more effective treatments that maximize the potential of these immune cells in combating cancer. As the field of immunotherapy continues to advance, the ability to address T cell exhaustion could lead to a significant improvement in patient outcomes and overall survival rates.
The collaboration between Dana-Farber Cancer Institute and NYU Grossman School of Medicine demonstrates the importance of interdisciplinary research in the fight against cancer. As more information is uncovered about the role of mSWI/SNF complexes in T cell exhaustion, researchers may also find applications in treating other diseases where immune system function is critical. This discovery marks a major step forward in the development of more powerful, targeted therapies that can improve the lives of countless patients battling cancer and other challenging diseases.