How to find a therapeutic TCR

The clinical success of cellular therapy with TCR-engineered T cells relies on the infused living drug's ability to activate and sustain a potent immune response against the target cells. T cell activation begins with the recognition of peptides presented by Major Histocompatibility Complex molecules (pMHC) on the target cells through the TCR. The subsequent triggering of the TCR signaling cascade culminates in the production of effector molecules, which are responsible for specific cell killing. However, only a small fraction of the TCR repertoire that recognizes a certain antigen can fully engage a T cell throughout all these steps. This primarily depends on the strength of the TCR:pMHC interaction, known as ‘TCR avidity’. Our goal is to develop functional screenings and in vitro assays for the high-throughput evaluation of TCR avidity and overall potency of TCR-engineered T cells. Through this advancements, we aim to facilitate a rapid selection of clinically relevant TCRs.