A modular synthetic DNA template platform for rapid generation of TCR-encoding mRNA and streamlined validation of cognate TCR–epitope reactivity
Abstract
The interaction between T-cell receptors (TCRs) and their cognate ligands plays an important role in the regulation of the adaptive immune system as this is key in inducing immune responses in cancer, infectious and autoimmune diseases. As identification of a cognate TCR relies on laborious experimental validation, we propose the use of a synthetic DNA template assembly approach for the rapid generation of TCR encoding in vitro transcribed (IVT) mRNA, enabling mRNA-based screening. We show antigen-specific T-cell activation of human CD8+ T cells after delivery of TCR encoding mRNA and coculture with antigen presenting cells, presenting the cognate antigen/human leukocyte antigen (HLA) complex. Additionally, we demonstrated functionality of CD8+ T cells expressing an mRNA delivered, MAGEA1/HLA-A*02:01 cognate TCR, showing in vitro killing of MAGEA1+ HLA-A*02:01+ non-small cell lung cancer cells. This work showcases a fast platform for TCR-mRNA generation, facilitating TCR functionality and reactivity validation in personalized in vitro screening assays.
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BibTeX
@article{esprit2026modular,
title = {{A modular synthetic DNA template platform for rapid generation of TCR-encoding mRNA and streamlined validation of cognate TCR–epitope reactivity}},
author = {Arthur Esprit and Dorien Autaers and Giada Bertazzon and Wout de Mey and Pieter Plattiau and Kirsten De Ridder and Cleo Goyvaerts and Kris Thielemans and Karine Breckpot and Lorenzo Franceschini},
journal = {Frontiers in Immunology},
year = {2026},
month = nov,
doi = {10.3389/fimmu.2026.1933354},
url = {https://www.frontiersin.org/articles/10.3389/fimmu.2026.1933354},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - A modular synthetic DNA template platform for rapid generation of TCR-encoding mRNA and streamlined validation of cognate TCR–epitope reactivity
AU - Arthur Esprit
AU - Dorien Autaers
AU - Giada Bertazzon
AU - Wout de Mey
AU - Pieter Plattiau
AU - Kirsten De Ridder
AU - Cleo Goyvaerts
AU - Kris Thielemans
AU - Karine Breckpot
AU - Lorenzo Franceschini
PY - 2026
DA - 2026/11/03
JO - Frontiers in Immunology
DO - 10.3389/fimmu.2026.1933354
UR - https://www.frontiersin.org/articles/10.3389/fimmu.2026.1933354
AB - The interaction between T-cell receptors (TCRs) and their cognate ligands plays an important role in the regulation of the adaptive immune system as this is key in inducing immune responses in cancer, infectious and autoimmune diseases. As identification of a cognate TCR relies on laborious experimental validation, we propose the use of a synthetic DNA template assembly approach for the rapid generation of TCR encoding in vitro transcribed (IVT) mRNA, enabling mRNA-based screening. We show antigen-specific T-cell activation of human CD8+ T cells after delivery of TCR encoding mRNA and coculture with antigen presenting cells, presenting the cognate antigen/human leukocyte antigen (HLA) complex. Additionally, we demonstrated functionality of CD8+ T cells expressing an mRNA delivered, MAGEA1/HLA-A*02:01 cognate TCR, showing in vitro killing of MAGEA1+ HLA-A*02:01+ non-small cell lung cancer cells. This work showcases a fast platform for TCR-mRNA generation, facilitating TCR functionality and reactivity validation in personalized in vitro screening assays.
SN - 1664-3224
ER -