Pioneering the Future of Cancer Immunotherapy: A New Era of Synthetic Immunology through Computational Modeling.

Chimeric Antigen Receptor (CAR) T-cell immunotherapy has revolutionized the treatment of hematological malignancies. However, its application to solid tumors has been hindered by poor specificity and potential toxicity to healthy tissues. To address these limitations, we developed an integrated approach combining a high-throughput robotic platform with mathematical modeling to systematically evaluate and optimize T-cell function. This novel approach enabled us to uncover previously unknown signaling crosstalk within CAR T-cells, leading to the development of an optimized CAR design. Our enhanced CAR T-cell platform demonstrates significantly improved anti-tumor activity while minimizing toxicity to healthy tissues. These findings highlight the power of computational modeling in simulating immune cell behaviors and provide a robust framework for designing more precise and effective cancer immunotherapies. (Presented at the 2015th Meeting, December 6th, 2024).