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- W4308398380 abstract "<h3>Background</h3> T cell receptor (TCR)-based therapeutics have displayed clinical proof-of-concept, however challenges remain to robustly identify both novel targets and therapeutically active TCRs against endogenous targets. <h3>Methods</h3> Here, we have developed a multi-plexed platform to efficiently identify novel TCRs towards non-mutated, tumor specific targets. We have developed a functional expansion protocol, combined with single cell sequencing, that enables the discovery of diverse TCRs in both function and sequence to multiple targets simultaneously. <h3>Results</h3> These novel TCRs are highly sensitive, with sub-nanomolar EC50s. Furthermore, these novel TCRs display in vitro killing of target-bearing cells. To interrogate the specificity of these TCRs, we utilized 3T-TRACE, a highly diverse pHLA-target library platform to identify potential cross-reactive peptides that could identify potential liabilities pre-clinically. We find that although sequence distinct TCRs display the same on-target reactivity, they vary considerably in their cross-reactivity. <h3>Conclusions</h3> Altogether, we have developed a robust platform to identify and select therapeutically active TCRs for TCR-T based therapy." @default.
- W4308398380 created "2022-11-11" @default.
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- W4308398380 date "2022-11-01" @default.
- W4308398380 modified "2023-10-07" @default.
- W4308398380 title "403 Rapid and multiplexed identification of novel TCRs for TCR-T cell therapy" @default.
- W4308398380 doi "https://doi.org/10.1136/jitc-2022-sitc2022.0403" @default.
- W4308398380 hasPublicationYear "2022" @default.
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