T cell engagers convert acute tumor killing into endogenous vaccination
- 1Institut Pasteur
Abstract
T cell engagers (TCEs) redirect T cells to kill tumors by cross-linking CD3{varepsilon} to a tumor antigen, independently of T cell receptor specificity. Some patients achieve remissions that persist long after drug clearance, but whether TCEs can couple acute cytotoxicity to the generation of lasting adaptive immunity remains unknown. Here, using an immunocompetent mouse model for clinical-grade human TCEs, we show that TCE-mediated killing initiates an endogenous vaccination cascade. Intravital two-photon imaging reveals a perforin-dependent cytotoxic wave that peaks within 24 hours, then subsides despite massive T cell accumulation. Single-cell transcriptomics and adoptive transfers demonstrate that memory CD8 T cells, the principal effector reservoir in mouse and human, transit through a progenitor-like state before differentiating into cytotoxic effectors with recall competence. Crucially, tumor lysis fuels cross-priming of tumor-specific CD8 T cells by XCR1 type 1 conventional dendritic cells, a cDC1-dependent step essential for durable tumor control and protective memory upon rechallenge.
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BibTeX
@misc{lecuit2026cell,
title = {{T cell engagers convert acute tumor killing into endogenous vaccination}},
author = {M. M. Lecuit and B. Corre and Z. Garcia and F. Lemaitre and A. Vaysse and R. Alonso and C. Goudot and B. Arnaud and L. C. Feldmann and C. Moraes Cabe and V. Seffer and P. Guermonprez and C. L. Grandjean and M. V. Guerin and P. Bousso},
howpublished = {bioRxiv},
year = {2026},
month = oct,
doi = {10.64898/2026.10.06.756695},
url = {https://www.biorxiv.org/content/10.64898/2026.10.06.756695v1},
note = {CC BY-NC-ND},
}
RIS
TY - UNPB
TI - T cell engagers convert acute tumor killing into endogenous vaccination
AU - M. M. Lecuit
AU - B. Corre
AU - Z. Garcia
AU - F. Lemaitre
AU - A. Vaysse
AU - R. Alonso
AU - C. Goudot
AU - B. Arnaud
AU - L. C. Feldmann
AU - C. Moraes Cabe
AU - V. Seffer
AU - P. Guermonprez
AU - C. L. Grandjean
AU - M. V. Guerin
AU - P. Bousso
PY - 2026
DA - 2026/10/06
PB - bioRxiv
DO - 10.64898/2026.10.06.756695
UR - https://www.biorxiv.org/content/10.64898/2026.10.06.756695v1
AB - T cell engagers (TCEs) redirect T cells to kill tumors by cross-linking CD3{varepsilon} to a tumor antigen, independently of T cell receptor specificity. Some patients achieve remissions that persist long after drug clearance, but whether TCEs can couple acute cytotoxicity to the generation of lasting adaptive immunity remains unknown. Here, using an immunocompetent mouse model for clinical-grade human TCEs, we show that TCE-mediated killing initiates an endogenous vaccination cascade. Intravital two-photon imaging reveals a perforin-dependent cytotoxic wave that peaks within 24 hours, then subsides despite massive T cell accumulation. Single-cell transcriptomics and adoptive transfers demonstrate that memory CD8 T cells, the principal effector reservoir in mouse and human, transit through a progenitor-like state before differentiating into cytotoxic effectors with recall competence. Crucially, tumor lysis fuels cross-priming of tumor-specific CD8 T cells by XCR1 type 1 conventional dendritic cells, a cDC1-dependent step essential for durable tumor control and protective memory upon rechallenge.
ER -