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By harnessing our immune system’s T cells, immunotherapies have revolutionized how we battle cancer and treat disease. The next-generation of immunotherapies is using our immune system's natural T-cell receptors (TCRs) to create highly effective precision medicines that further improve patient outcomes. These therapies have already cured patients of cancer in early-stage clinical studies, but before their potential can be widely realized, the commercial development of therapeutic-TCRs must be de-risked by solving the challenge of detecting off-target reactivity. 

Due to how our immune system evolved, therapeutic-TCRs have the potential for off-target reactivity that can compromise patient health. As such, companies developing T cell receptor based immunotherapies must extensively test to ensure their therapies react specifically to therapeutic targets without damaging healthy tissue. Unfortunately, the techniques to do this are costly, laborious, and have failed to ensure patient safety.  

Led by Dr. Robert Holt, the researchers at BC Cancer will advance and validate their platform technology, Tope-seq, to address this critical, unmet industry need. They propose to demonstrate Tope-seq’s ability to: a) detect off-target reactivity efficiently and effectively, through a retrospective analysis of a therapeutic TCR with known off-target reactivity; and b), discover safe and novel therapeutic TCRs. Data generated will be critical to prove to commercial partners that Tope-seq can improve their ability to address the challenge of off-target reactivity, increasing the likelihood that TCR-based therapies achieve success in clinical trials and ultimately, save lives.