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Tope-seq: A high-throughput platform to discover and characterize T-cell receptor reactivity for advancing safe and effective immunotherapies

  • Project Leaders: Rob Holt
  • Institutions: BC Cancer (Previously BC Cancer Agency (BCCA))
  • Budget: $250000
  • Program/Competition: Pilot Innovation Fund
  • Genome Centre(s): Genome British Columbia
  • Fiscal Year: 2021
  • Status: Closed

By harnessing our immune system’s T-cells, immunotherapies have revolutionized how we battle cancer and treat disease. The next-generation of immunotherapies are using our immune system's natural T-cell receptors (TCRs) to create highly effective precision medicines that further improve patient outcomes. While extremely promising, therapeutic-TCRs may have off-target reactivity with healthy tissue, leading to patient complications and potentially death. These therapies have already cured patients of cancer in some early-stage clinical studies, however, 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. Unfortunately, the techniques to do this are costly, laborious and have failed so far to ensure patient safety.  

Led by Dr. Robert Holt, the researchers at BC Cancer have advanced and validated their platform technology, Tope-seq, to address this critical, unmet industry need. As a proof-of-concept, the team illustrated that Tope-seq was able to efficiently and effectively identify off-target reactivity of a therapeutic-TCR with known off-target reactivity. This data illustrates to commercial partners that Tope-seq can improve the detection of off-target reactivity in the development of TCR-based therapies; preventing unsuccessful clinical trials and potential patient harm. In addition, the team have utilized Tope-seq to identify novel therapeutic TCRs for SARS-CoV-2. The Tope-seq technology advanced through this project has attracted commercial partners and advanced the growth of BC Cancer spin-off company, Immfinity Biotechnologies Inc.