CXCR3 on transferred T cells enables vaccine-boosted adoptive T-cell therapy in solid tumors
- 1Ludwig Institute for Cancer Research, Nuffield Department of Medicine, University of Oxford, Oxford, UK
Abstract
Adoptive T-cell therapy (ACT) has demonstrated marked clinical benefit in hematological malignancies but has limited efficacy against solid tumors. Cancer vaccines can improve ACT, but the mechanisms underlying this combination are poorly understood. Here, we combined ACT with chimpanzee adenovirus ChAdOx1 (ChAd) and modified vaccinia Ankara (MVA) encoding tumor antigens. Whereas PD1 blockade failed to improve ACT, the combination with ChAd/MVA vaccination drove durable regression of established tumors, correlating with expansion of tumor-reactive T cells in lymphoid organs and increased tumor infiltration by T cells. Mechanistically, ChAd priming induced CXCR3 ligands (CXCL10 and CXCL9) in the vaccine-draining lymph node, thereby recruiting transferred T cells to this node independently of cognate antigen. CXCR3 expression on the transferred T cells, but not on host cells, was required for the anti-tumor effect of the combination therapy and favored T-cell accumulation in the vaccine-draining lymph node and the tumor. These findings identify CXCR3 on the transferred T cells as a determinant of ACT plus vaccination synergy and provide a rationale for combining viral-vector vaccines with TCR-T therapies, and for selecting or engineering T cells to retain CXCR3 expression.
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BibTeX
@misc{almeida2026cxcr3,
title = {{CXCR3 on transferred T cells enables vaccine-boosted adoptive T-cell therapy in solid tumors}},
author = {V. Pereira Almeida and L. C. Garner and S. Abdel Malak and A. Wicki and J. McAuliffe and L. Noblecourt and S. Panetti and E. E. Steffke and A. Bhandari and L. Yong and A. Amini and C. Hutchings and F. Andreata and Y. Yang and A. Gerard and M. Iannacone and R. A. Fernandes and P. Klenerman and B. Van den Eynde and C. S. K. Leung},
howpublished = {bioRxiv},
year = {2026},
month = oct,
doi = {10.64898/2026.10.04.753375},
url = {https://www.biorxiv.org/content/10.64898/2026.10.04.753375v1},
note = {CC BY},
}
RIS
TY - UNPB
TI - CXCR3 on transferred T cells enables vaccine-boosted adoptive T-cell therapy in solid tumors
AU - V. Pereira Almeida
AU - L. C. Garner
AU - S. Abdel Malak
AU - A. Wicki
AU - J. McAuliffe
AU - L. Noblecourt
AU - S. Panetti
AU - E. E. Steffke
AU - A. Bhandari
AU - L. Yong
AU - A. Amini
AU - C. Hutchings
AU - F. Andreata
AU - Y. Yang
AU - A. Gerard
AU - M. Iannacone
AU - R. A. Fernandes
AU - P. Klenerman
AU - B. Van den Eynde
AU - C. S. K. Leung
PY - 2026
DA - 2026/10/04
PB - bioRxiv
DO - 10.64898/2026.10.04.753375
UR - https://www.biorxiv.org/content/10.64898/2026.10.04.753375v1
AB - Adoptive T-cell therapy (ACT) has demonstrated marked clinical benefit in hematological malignancies but has limited efficacy against solid tumors. Cancer vaccines can improve ACT, but the mechanisms underlying this combination are poorly understood. Here, we combined ACT with chimpanzee adenovirus ChAdOx1 (ChAd) and modified vaccinia Ankara (MVA) encoding tumor antigens. Whereas PD1 blockade failed to improve ACT, the combination with ChAd/MVA vaccination drove durable regression of established tumors, correlating with expansion of tumor-reactive T cells in lymphoid organs and increased tumor infiltration by T cells. Mechanistically, ChAd priming induced CXCR3 ligands (CXCL10 and CXCL9) in the vaccine-draining lymph node, thereby recruiting transferred T cells to this node independently of cognate antigen. CXCR3 expression on the transferred T cells, but not on host cells, was required for the anti-tumor effect of the combination therapy and favored T-cell accumulation in the vaccine-draining lymph node and the tumor. These findings identify CXCR3 on the transferred T cells as a determinant of ACT plus vaccination synergy and provide a rationale for combining viral-vector vaccines with TCR-T therapies, and for selecting or engineering T cells to retain CXCR3 expression.
ER -