The Combination of Oncolytic Virus and Antibody Blockade of TGF-β Enhances the Efficacy of αvβ6-Targeting CAR T Cells Against Pancreatic Cancer in an Immunocompetent Model
Simple Summary
Abstract
1. Introduction
2. Materials and Methods
2.1. Cells and Cell Culture
2.2. Cloning of a Murine αvβ6-Targeted CAR into the MSGV Gammaretroviral Vector
2.3. Murine CAR T Cells Production
2.4. Flow Cytometry
2.5. Cytotoxicity Assay of the CAR-T Cells
2.6. Cytokine Release Analysis
2.7. Cytotoxicity Assay of the Virus
2.8. Viral Infection and Replication Assay
2.9. Animal Experiments
2.10. IVIS Bioluminescence Imaging
2.11. Tissue Harvesting and Immunohistochemistry
3. Results
3.1. Murine A20FMDV2 Peptide-Based CAR T Cells Demonstrate a Specific Anti-Tumour Effect Toward Pancreatic Cancer Cells Overexpressing Integrin αvβ6
3.2. An Optimized Process for the Production and Long-Term Cryopreservation Storage of Murine CAR T Cells
3.3. Oncolytic Vaccinia Virus Combined with TGF-β Antibody Improves the Efficacy of CAR T Cell Therapy in an Immunocompetent Pancreatic Cancer Model
3.4. Triple Combination Therapy Controls Orthotopic Tumour Growth and Attenuates Metastasis in Pancreatic Cancer Within an Immunocompetent Model When Extending IL-2 Supplementation
3.5. The Triple Therapy Enhances CAR T Cell Efficacy by Improving T Cell Infiltration and Persistence in Pancreatic Cancer
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Zhao, Z.; Cutmore, L.C.; Baleeiro, R.B.; Hartlebury, J.J.; Brown, N.; Chard-Dunmall, L.; Lemoine, N.; Wang, Y.; Marshall, J.F. The Combination of Oncolytic Virus and Antibody Blockade of TGF-β Enhances the Efficacy of αvβ6-Targeting CAR T Cells Against Pancreatic Cancer in an Immunocompetent Model. Cancers 2025, 17, 1534. https://doi.org/10.3390/cancers17091534
Zhao Z, Cutmore LC, Baleeiro RB, Hartlebury JJ, Brown N, Chard-Dunmall L, Lemoine N, Wang Y, Marshall JF. The Combination of Oncolytic Virus and Antibody Blockade of TGF-β Enhances the Efficacy of αvβ6-Targeting CAR T Cells Against Pancreatic Cancer in an Immunocompetent Model. Cancers. 2025; 17(9):1534. https://doi.org/10.3390/cancers17091534
Chicago/Turabian StyleZhao, Zuoyi, Lauren C. Cutmore, Renato B. Baleeiro, Joseph J. Hartlebury, Nicholas Brown, Louisa Chard-Dunmall, Nicholas Lemoine, Yaohe Wang, and John F. Marshall. 2025. "The Combination of Oncolytic Virus and Antibody Blockade of TGF-β Enhances the Efficacy of αvβ6-Targeting CAR T Cells Against Pancreatic Cancer in an Immunocompetent Model" Cancers 17, no. 9: 1534. https://doi.org/10.3390/cancers17091534
APA StyleZhao, Z., Cutmore, L. C., Baleeiro, R. B., Hartlebury, J. J., Brown, N., Chard-Dunmall, L., Lemoine, N., Wang, Y., & Marshall, J. F. (2025). The Combination of Oncolytic Virus and Antibody Blockade of TGF-β Enhances the Efficacy of αvβ6-Targeting CAR T Cells Against Pancreatic Cancer in an Immunocompetent Model. Cancers, 17(9), 1534. https://doi.org/10.3390/cancers17091534