Viscoelastic synthetic antigen-presenting cells for augmenting the potency of cancer therapies.

Cancer immunotherapy is a promising approach that uses the body's own immune system to fight cancer. One important type of immunotherapy, known as CAR-T cell therapy, involves collecting a patient's immune cells, called T cells, and genetically modifying them to recognize and attack cancer cells. However, producing enough highly effective T cells that can survive and continue fighting cancer over time remains a major challenge. To address this problem, we developed a new type of artificial cell, called a synthetic viscoelastic T-cell-activating cell (SynVAC), that closely mimics the physical properties and functions of natural immune cells responsible for activating T cells. Unlike conventional artificial particles, which are typically hard or simply elastic, SynVACs are soft, flexible, and able to change shape in response to mechanical forces, similar to living cells. Using an advanced manufacturing technology, we can efficiently produce large numbers of these artificial cells with precisely controlled properties. Our research showed that SynVACs significantly improved the growth and activation of T cells, particularly those responsible for directly killing cancer cells. They also reduced the formation of immune cells that can suppress the body's ability to fight cancer. Importantly, SynVACs improved the efficiency of genetically modifying T cells, with approximately 90% of the resulting cells successfully expressing the engineered cancer-targeting receptor. In addition, this approach increased the production of long-lasting memory T cells, which may help maintain protection against cancer and reduce the likelihood of recurrence. In animal studies, CAR-T cells prepared using SynVACs successfully eliminated lymphoma cells, slowed ovarian tumor growth, and remained active in the body for longer periods. These findings suggest that SynVACs could help overcome important limitations of current CAR-T cell manufacturing methods. Overall, our study demonstrates that the physical properties of artificial cells play a critical role in preparing effective cancer-fighting immune cells. By better recreating the natural environment in which T cells become activated, SynVACs offer a promising strategy for improving the strength, durability, and long-term effectiveness of cancer immunotherapies. Further research is needed to determine whether these benefits can be achieved safely and effectively in patients.