PAIR-Scan: Single-step identification of highly potent TCR-neoantigen pairs through library-on-library screening
- 1The Netherlands Cancer Institute
Abstract
Tumors contain a mixture of T cells with bystander reactivities and reactivities towards different, frequently patient-specific, cancer (neo)antigens. The one-step identification of highly active TCR-antigen pairs in human tumors would be valuable, both as a monitoring tool and to boost T cell reactivities of interest. Here, we develop PAIR-Scan, an HLA-agnostic library-on-library screening technology that identifies functionally active TCR-neoantigen pairs among tens of thousands of candidate pairs in a single step. We demonstrate the value of PAIR-Scan on a range of tumor samples and for the direct identification of TCR-recognized minimal peptides. In addition, we demonstrate that PAIR-Scan correctly ranks TCRs reactive to the same antigen by their relative tumor-killing efficiency. Together, these data demonstrate the value of PAIR-Scan for both the dissection of T cell responses in clinical samples and to generate large-scale datasets for the development of predictive models of TCR reactivity.
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BibTeX
@misc{messemaker2026pairscan,
title = {{PAIR-Scan: Single-step identification of highly potent TCR-neoantigen pairs through library-on-library screening}},
author = {M. Messemaker and C. A. Richterich and J. Wenner and Y. Ma and Z. Moravec and R. Voogd and M. Mussmann and S. de Paauw and B. P. Y. Kwee and J. Geerligs and B. Morris and Y. Winkler and B. O. Springer and F. T. B. T. van den Brekel and J. Urbanus and A. Guislain and N. Alfaiate and F. van Diepen and M. van Baalen and B. Nicolet and J. B. A. G. Haanen and C. J. Wu and J. Huuhtanen and W. Scheper and T. N. Schumacher},
howpublished = {bioRxiv},
year = {2026},
month = sep,
doi = {10.64898/2026.09.07.749948},
url = {https://www.biorxiv.org/content/10.64898/2026.09.07.749948v1},
note = {CC BY-NC-ND},
}
RIS
TY - UNPB
TI - PAIR-Scan: Single-step identification of highly potent TCR-neoantigen pairs through library-on-library screening
AU - M. Messemaker
AU - C. A. Richterich
AU - J. Wenner
AU - Y. Ma
AU - Z. Moravec
AU - R. Voogd
AU - M. Mussmann
AU - S. de Paauw
AU - B. P. Y. Kwee
AU - J. Geerligs
AU - B. Morris
AU - Y. Winkler
AU - B. O. Springer
AU - F. T. B. T. van den Brekel
AU - J. Urbanus
AU - A. Guislain
AU - N. Alfaiate
AU - F. van Diepen
AU - M. van Baalen
AU - B. Nicolet
AU - J. B. A. G. Haanen
AU - C. J. Wu
AU - J. Huuhtanen
AU - W. Scheper
AU - T. N. Schumacher
PY - 2026
DA - 2026/09/07
PB - bioRxiv
DO - 10.64898/2026.09.07.749948
UR - https://www.biorxiv.org/content/10.64898/2026.09.07.749948v1
AB - Tumors contain a mixture of T cells with bystander reactivities and reactivities towards different, frequently patient-specific, cancer (neo)antigens. The one-step identification of highly active TCR-antigen pairs in human tumors would be valuable, both as a monitoring tool and to boost T cell reactivities of interest. Here, we develop PAIR-Scan, an HLA-agnostic library-on-library screening technology that identifies functionally active TCR-neoantigen pairs among tens of thousands of candidate pairs in a single step. We demonstrate the value of PAIR-Scan on a range of tumor samples and for the direct identification of TCR-recognized minimal peptides. In addition, we demonstrate that PAIR-Scan correctly ranks TCRs reactive to the same antigen by their relative tumor-killing efficiency. Together, these data demonstrate the value of PAIR-Scan for both the dissection of T cell responses in clinical samples and to generate large-scale datasets for the development of predictive models of TCR reactivity.
ER -