Messemaker and Kwee et al. developed a TCR rapid assembly platform (T-RAP) that could be used to evaluate TCR reactivity acir.org/weekly-dige...
@schumacher-lab.bsky.social
@nkinl.bsky.social
Schumacher Lab
@schumacher-lab.bsky.social
We use a technology-based approach to understand how our T cells recognize cancer. @nkinl.bsky.social | Tweets from lab members
Co-led with Connor Richterich. Thanks to our incredible team and funders, especially the @knaw-nl.bsky.social Stevin prize and @cancergrand.bsky.social MATCHMAKERS team. Thanks also to @nkinl.bsky.social and @oncodeinstitute.bsky.social hosting this research, and our supervisor Ton Schumacher.
What are some of the use cases that are enabled by PAIR-Scan's scale and capacity for potency ranking? (7/7)
What about precision? Across PAIR-Scan screens, top-ranked pairs validate as reactive and tested lower-ranked pairs as non-reactive, showing near-perfect separation, so users rarely waste validation effort on false positives. (6/7)
Can PAIR-Scan rank TCRs reactive to the same neoantigen by their potency? Yes ✅, PAIR-Scan enrichment ranks TCRs by their functional killing activity. (5/7)
Proof-of-concept: Can PAIR-Scan identify reactive TCR–neoantigen among 40,000 candidate CD8+ TIL TCR and candidate neoantigen combinations? Yes ✅. (4/7)
As TCR signalling drives cell adhesion & Ca2+ flux, we reasoned Ca2+ flux T-B doublets could inform us on reactive pairs. Furthermore, as duration of Ca2+ flux reflects TCR signal strength, we reasoned that it may be feasible to even rank TCR–antigen pairs by their potency (3/7)
Others and we @schumacher-lab.bsky.social built ‘one-sided’ screening tech to identify T cell-recognized antigens or to identify antigen-reactive TCRs. But scalable, cell-based library-on-library methods to directly identify interacting TCR–antigen pairs have been lacking.
(2/7)
Hi, we would like to introduce PAIR-Scan, an HLA-agnostic library-on-library screening technology that can identify reactive TCR–antigen pairs with optimal killing activity among up to ~100,000 possible candidate pairs in a single-step.
🧵(1/7)
www.biorxiv.org/content/10.6...
