T cells engineered to express a TCR of interest are mixed with a genome-wide library of target cells, each of which expresses a different protein fragment. In each target cell, the protein fragment is processed by the proteasome and the resulting peptides are displayed naturally on cell-surface MHC proteins. If a T cell recognizes the peptide-MHC complex on a target cell, it attempts to kill the target cell, thereby activating a fluorescent reporter in the target cell. By sorting for fluorescent target cells and sequencing their expression cassettes, the natural target(s) of the T cell are revealed.

TARGET ID PLATFORM IDENTIFIES THE NATURAL TARGETS OF TCRs

To ensure broad target coverage, TScan’s proprietary libraries comprise hundreds of thousands of protein fragments spanning every human protein and all common single nucleotide polymorphisms (SNPs). They also include elements that are unique to cancer cells, and thus particularly interesting as targets: common driver mutations in cancer, endogenous retroviral elements, and a large collection of sequences that are not translated in normal tissue but are frequently translated in human cancers. Our libraries are constructed using a tiling pattern of overlapping fragments, ensuring complete coverage of every targeted sequence. TScan is using this technology to identify new targets for TCR therapy and to ensure the safety of every therapeutic TCR by fully characterizing all potential off-target interactions.

TSCAN GENOME-WIDE LIBRARY