CD28 Co-Stimulus Achieves Superior CAR T Cell Effector Function against Solid Tumors Than 4-1BB Co-Stimulus
Abstract
:Simple Summary
Abstract
1. Introduction
2. Materials and Methods
2.1. Cell Lines and Culture Conditions
2.2. CAR Construct Generation
2.3. Gamma-Retroviral and Lentiviral Vector Production, Transduction and CAR T Cell Generation
2.4. Flow Cytometry
2.5. Bioluminescence-Based Cytotoxicity and Cytokine Release Assays
2.6. In Vivo Studies
2.7. Tumor-Infiltrating T Cell (TIL) Isolation
2.8. Statistical Analysis
3. Results
3.1. Short Spacer L1CAM-Specific CAR T Cells with CD28 Signaling Prolonged Survival of SK-N-BE(2) Tumor-Bearing Mice
3.2. Anti-Tumor Effect of L1CAM-Specific CAR T Cells Correlates with T Cell Expansion at the Tumor Site
3.3. Superior Function of Human L1CAM-SS-28/ζ CAR T Cells Is Confirmed in a PDX Mouse Model
3.4. HER2-Specific CAR T Cells with CD28 Co-Stimulation Possess Higher Effector Function
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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Textor, A.; Grunewald, L.; Anders, K.; Klaus, A.; Schwiebert, S.; Winkler, A.; Stecklum, M.; Rolff, J.; Henssen, A.G.; Höpken, U.E.; et al. CD28 Co-Stimulus Achieves Superior CAR T Cell Effector Function against Solid Tumors Than 4-1BB Co-Stimulus. Cancers 2021, 13, 1050. https://doi.org/10.3390/cancers13051050
Textor A, Grunewald L, Anders K, Klaus A, Schwiebert S, Winkler A, Stecklum M, Rolff J, Henssen AG, Höpken UE, et al. CD28 Co-Stimulus Achieves Superior CAR T Cell Effector Function against Solid Tumors Than 4-1BB Co-Stimulus. Cancers. 2021; 13(5):1050. https://doi.org/10.3390/cancers13051050
Chicago/Turabian StyleTextor, Ana, Laura Grunewald, Kathleen Anders, Anika Klaus, Silke Schwiebert, Annika Winkler, Maria Stecklum, Jana Rolff, Anton G. Henssen, Uta E. Höpken, and et al. 2021. "CD28 Co-Stimulus Achieves Superior CAR T Cell Effector Function against Solid Tumors Than 4-1BB Co-Stimulus" Cancers 13, no. 5: 1050. https://doi.org/10.3390/cancers13051050