Protein Engineering Aids Chimeric Antigen Receptor Design

Chimeric antigen receptor (CAR) directed T-cell therapy has reenergized the cancer immunotherapy field with remarkable success treating patients with multiple types of leukemia and lymphoma in the clinic. Two such therapies, Kymriah and Yescarta, were recently approved by the FDA for widespread clinical use. On the heels of this success, the immunotherapy field has begun to apply this technology to treat many different types of cancers. The generation of new chimeric antigen receptors for these applications is empirical and inefficient, requiring low-throughput experiments to validate activity. Many of the potential pitfalls in this process stem from the molecular design of these CARs, which can lead to undesirable characteristics that decrease therapeutic impact. I am using engineering principles and high-throughput screening techniques to aid CAR design and rapidly screen hundreds of millions to billions of variant molecules capable of mediating T cell recognition for appropriate disease-specific interactions. Overall, this work will streamline the CAR development process through a suite of efficient techniques, as well as open new avenues for the development of novel CARs as additional immunotherapy targets in different cancers are discovered. Additionally, CARs developed through these projects will progress toward clinical translation, turning these fundamental scientific advances into technologies with a positive impact on patients and their families.