Enhancing Activity and Stability of Cytokines for Immune Cell Therapy Workflows Using Advanced Protein Engineering 3247

Abstract Description Recombinant cytokines are indispensable reagents in the manufacture of immune-based therapies. Dependable and stable reagents are required for consistency in culture conditions and standardization of developmental procedures to produce efficient and cost-effective therapies. Although improvements have been made through manufacturing and cell process development, little attention has been given to how enhancing recombinant proteins could alleviate common pinch points like operational and process development costs in immune cell therapy. In this study, we utilized Artificial Intelligence (AI)/predictive analytics to develop hyper-stable and hyper-active cytokines for TIL, T/NK cell workflows. Our method improved upon the unstable regions in IL-2 while maintaining efficient engagement and activation of the IL-2βγ receptors. The resulting Heat IL-2 provides superior heat stability, duration in media, and delivers comparable or greater results in purified CD4/CD8 T cell or TIL outgrowth assays compared to standard IL-2 proteins. Furthermore, we used cutting-edge protein engineering techniques to enhance the performance of other commonly used gamma chain cytokines, ideal for extended immune cell workflows, such as TIL and allogeneic cell therapies. Overall, our study demonstrates the importance of protein engineering for enhancing the performance of cytokines in operational and immune cell process development, delivering efficient and cost-effective immune cell manufacturing. Funding Sources N/A Topic Categories Cytokines and Chemokines and Their Receptors (CCR)