Immunotargeting of Cervical Cancer Cells with the Adaptor CAR T-Cell Platform RevCAR
7 affiliations
- 1Institute of Radiopharmaceutical Cancer Research, Helmholtz-Zentrum Dresden-Rossendorf (HZDR), 01307 Dresden, Germany
- 2School of Medicine, Department of Basic Sciences, Universidad Industrial de Santander, Bucaramanga 680002, Colombia
- 3Mildred Scheel Early Career Center, Faculty of Medicine Carl Gustav Carus, TUD Dresden University of Technology, 01062 Dresden, Germany
- 4German Cancer Consortium (DKTK), Partner Site Dresden, 01062 Dresden, Germany
- 5National Center for Tumor Diseases (NCT), NCT/UCC Dresden, A Partnership Between DKFZ, Faculty of Medicine and University Hospital Carl Gustav Carus, TUD Dresden University of Technology & Helmholtz-Zentrum Dresden-Rossendorf (HZDR), 01307 Dresden, Germany
- 6Brandenburg Medical School and Faculty of Health Science, Institute for Translational Medicine, 14770 Brandenburg, Germany
- 7Institute of Pathology, Section Immunopathology, Martin-Luther-University Halle-Wittenberg, 06112 Halle, Germany
Abstract
The Prostate Stem Cell Antigen (PSCA) is not only overexpressed in prostate cancer (PC) but also in many other tumors, including cervical cancer (CC). The adaptor chimeric antigen receptor (CAR) platform RevCAR can be used for immunotargeting of PSCA-expressing tumor cells. We found that the CC cell line SiHa natively expresses PSCA. The expression was sufficient for redirection of RevCAR T-cells using recently described RevCAR target modules (RevTMs) directed against PSCA. Like almost all PC cell lines, however, SiHa cells also downregulate their PSCA expression in cell culture. To overcome this limitation, we established artificially PSCA-overexpressing SiHa cells. Retargeting of RevCAR T-cells strictly depends on PSCA-directed RevTMs and PSCA-expressing target cells. It leads to (i) upregulation of CD69, Perforin and Granzyme B, (ii) lysis of target cells with EC50 values in the picomolar range, and (iii) cytokine secretion of IFN-γ, TNF-α, GM-CSF and IL-2. Phenotypic analysis shows a prominent increase in memory RevCAR T-cells but only a slight increase in exhausted cells, indicating a low level of tonic signaling of RevCAR T-cells. Together, our data supports an efficient and safe immunotargeting of PSCA-expressing CC cells with the RevCAR technology.
Related
- An adaptor for feedback regulation of heme biosynthesis by a mitochondrial protease
- HPV E6/E7, O-GlcNAcylation and mitochondrial remodeling in cervical cancer: mechanistic links and translational opportunities
- An intrinsically disordered adaptor protein controls the size and composition of EGFR condensates on membranes
- Comparative Acetylation and Ubiquitination Profiling in Cervical Cancer-Cell Models Supports a Proposed Lysine-Fate Code
- Integrated multi-omics analysis reveals the molecular landscape and therapeutic strategies in Chinese cervical cancer patients
BibTeX
@article{jonescifuentes2026immunotargeting,
title = {{Immunotargeting of Cervical Cancer Cells with the Adaptor CAR T-Cell Platform RevCAR}},
author = {Nathalia Jones-Cifuentes and Claudia Arndt and Liliana R. Loureiro and Nicole Berndt and Alexandra von Jutrzenka-Trzebiatowski and Anja Feldmann and Jennifer Bachmann and Barbara Seliger and Bladimiro Rincon-Orozco and Michael Bachmann},
journal = {International Journal of Molecular Sciences},
year = {2026},
month = oct,
doi = {10.3390/ijms27219704},
url = {https://www.mdpi.com/1422-0067/27/21/9704},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Immunotargeting of Cervical Cancer Cells with the Adaptor CAR T-Cell Platform RevCAR
AU - Nathalia Jones-Cifuentes
AU - Claudia Arndt
AU - Liliana R. Loureiro
AU - Nicole Berndt
AU - Alexandra von Jutrzenka-Trzebiatowski
AU - Anja Feldmann
AU - Jennifer Bachmann
AU - Barbara Seliger
AU - Bladimiro Rincon-Orozco
AU - Michael Bachmann
PY - 2026
DA - 2026/10/29
JO - International Journal of Molecular Sciences
DO - 10.3390/ijms27219704
UR - https://www.mdpi.com/1422-0067/27/21/9704
AB - The Prostate Stem Cell Antigen (PSCA) is not only overexpressed in prostate cancer (PC) but also in many other tumors, including cervical cancer (CC). The adaptor chimeric antigen receptor (CAR) platform RevCAR can be used for immunotargeting of PSCA-expressing tumor cells. We found that the CC cell line SiHa natively expresses PSCA. The expression was sufficient for redirection of RevCAR T-cells using recently described RevCAR target modules (RevTMs) directed against PSCA. Like almost all PC cell lines, however, SiHa cells also downregulate their PSCA expression in cell culture. To overcome this limitation, we established artificially PSCA-overexpressing SiHa cells. Retargeting of RevCAR T-cells strictly depends on PSCA-directed RevTMs and PSCA-expressing target cells. It leads to (i) upregulation of CD69, Perforin and Granzyme B, (ii) lysis of target cells with EC50 values in the picomolar range, and (iii) cytokine secretion of IFN-γ, TNF-α, GM-CSF and IL-2. Phenotypic analysis shows a prominent increase in memory RevCAR T-cells but only a slight increase in exhausted cells, indicating a low level of tonic signaling of RevCAR T-cells. Together, our data supports an efficient and safe immunotargeting of PSCA-expressing CC cells with the RevCAR technology.
SN - 1422-0067
ER -