A Rational Designed Novel Bispecific Antibody for the Treatment of GBM
Abstract
:1. Introduction
2. Materials and Methods
2.1. Animal and Tumor Cell Lines
2.2. Protein Expression and Purification
2.3. Optimization of the Condition of the “BAPTS” Reaction
2.4. EGFRvIII-BsAb Characterization
2.5. Flow Cytometry
2.6. Binding of EGFRvIII-BsAb to EGFRvIII+ U87MG.ΔEGFR Cells
2.7. Binding of EGFRvIII-BsAb to CD3+ Jurkat Cells
2.8. Affinity Measurement of EGFRvIII-BsAb with Surface Plasmon Resonance (SPR)
2.9. CD3+ Jurkat Cells Recruited to EGFRvIII+ Tumor Cells
2.10. T-Cell Activation and Cytotoxic Cytokine Release in the Presence of Tumor Cells
2.11. EGFRvIII-BsAb Mediated Cytotoxicity against GBM Cells
2.12. Pharmacokinetics Analysis
2.13. Xenograft Studies
2.14. Animal Experiment Statement
2.15. Statistical Analysis
3. Results
3.1. Preparation and Purification of the EGFRvIII-BsAb with the BAPTS Platform
3.2. In Vitro Activity of the EGFRvIII-BsAb
3.2.1. Cellular Binding of the EGFRvIII-BsAb
3.2.2. EGFRvIII-BsAb Redirected T Cells to Tumor Cells
3.2.3. The EGFRvIII-BsAb Activated T Cells to Release Cytotoxic Cytokines
3.2.4. EGFRvIII-BsAb Mediated T Cells to Lyse Tumor Cells In Vitro
3.3. In Vivo Activity of the EGFRvIII-BsAb
3.3.1. Tumor Growth Inhibition in Immunocompromised Mice by the EGFRvIII-BsAb
3.3.2. Pharmacokinetic (PK) Analysis
4. Discussion
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Sun, R.; Zhou, Y.; Han, L.; Pan, Z.; Chen, J.; Zong, H.; Bian, Y.; Jiang, H.; Zhang, B.; Zhu, J. A Rational Designed Novel Bispecific Antibody for the Treatment of GBM. Biomedicines 2021, 9, 640. https://doi.org/10.3390/biomedicines9060640
Sun R, Zhou Y, Han L, Pan Z, Chen J, Zong H, Bian Y, Jiang H, Zhang B, Zhu J. A Rational Designed Novel Bispecific Antibody for the Treatment of GBM. Biomedicines. 2021; 9(6):640. https://doi.org/10.3390/biomedicines9060640
Chicago/Turabian StyleSun, Rui, Yuexian Zhou, Lei Han, Zhidi Pan, Jie Chen, Huifang Zong, Yanlin Bian, Hua Jiang, Baohong Zhang, and Jianwei Zhu. 2021. "A Rational Designed Novel Bispecific Antibody for the Treatment of GBM" Biomedicines 9, no. 6: 640. https://doi.org/10.3390/biomedicines9060640