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makeTCR: A Modular Platform for Rapid, Flexible, Scalable, Single-Step T Cell Receptor Synthesis

Hamberger, M.; Neuhoff, M.-T.; Pietrantonio, S. V.; Boschert, T.; Torres, C. M.; Errerd, A.; Tan, C. L.; Lindner, J. M.; Platten, M.; Green, E. W.

2025-07-23 immunology
10.1101/2025.04.27.647198 bioRxiv
Show abstract

Personalised cell therapies utilising T cell receptors (TCRs) show tremendous clinical promise, though TCR synthesis and validation techniques lag behind our ability to sequence TCR repertoires. To address this gap, we developed makeTCR: a flexible modular, scalable TCR cloning system that enables single-step, 100% fidelity assembly of {beta} and {gamma}{delta} TCRs into commonly used expression vectors. By implementing cell-free manufacturing, makeTCR enables patient-derived TCRs to be functionally validated within 48 hours. We provide an open-source, easily extensible, web-based graphical platform that integrates existing tools to simplify and standardise the manufacture of TCRs across all scales of synthesis.

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