A Novel Monoclonal Antibody against PD-1 for the Treatment of Viral Oncogene-Induced Tumors or Other Cancer
Abstract
:Simple Summary
Abstract
1. Introduction
2. Materials and Methods
2.1. Construction and Generation of P1801
2.2. BLI-Based P1801 Epitope Binning Assay
2.3. Direct Binding ELISA for the Assessment of Binding Specificity
2.4. Measurement of the Inhibition of PD-1/PD-L1 and PD-1/PD-L2 via Competitive Binding ELISA
2.5. In Vitro Affinity of P1801 for FcRn, C1q, and Human PD-1
2.6. In Vitro Antibody-Dependent Cell-Mediated Cytotoxicity (ADCC) Assay
2.7. In Vitro Complement-Dependent Cytotoxicity (CDC) Assay
2.8. In Vitro Receptor Occupancy Assay
2.9. Receptor Occupancy Assay in Cynomolgus Monkeys
2.10. In Vitro Cytokine Response Assay
2.11. PK, Immunogenicity, and Toxicokinetics of P1801 in Cynomolgus Monkeys
2.12. Antitumor Assessment in Mice
3. Results
3.1. Distinct Epitope Specificity of P1801 Compared to Pembrolizumab and Nivolumab
3.2. Molecular Properties of P1801
3.3. Binding Specificity and the Inhibition of Ligand Binding
3.4. Tissue Cross-Reactivity of P1801 in Humans and Cynomolgus Monkeys
3.5. In Vitro and In Vivo Pharmacodynamic Activity
3.6. PK, Immunogenicity, and Toxicokinetics of P1801 in Cynomolgus Monkeys
3.7. Antitumor Activity of P1801 in Mice
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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PK Parameters (First Dose) | 1 mg/kg n = 4 | 5 mg/kg n = 4 | 20 mg/kg n = 4 |
---|---|---|---|
Cmax (μg/mL) | |||
Mean | 37.0 | 186.0 | 746.0 |
SD | 3.11 | 35.5 | 89.9 |
Tmax (h) | |||
Mean | 1.00 | 1.00 | 0.50 |
SD | 1.15 | 1.15 | 1.00 |
T1/2 (h) | |||
Mean | 132.0 | 282.0 | 643.0 |
SD | 14.1 | 46.7 | 334.0 |
CL (mL/min/kg) | |||
Mean | 0.00248 | 0.00155 | 0.00168 |
SD | 0.000675 | 0.000308 | 0.000520 |
Vss (L/kg) | |||
Mean | 0.0398 | 0.0415 | 0.0631 |
SD | 0.00965 | 0.00513 | 0.00783 |
AUC0−last (h∗μg/mL) | |||
Mean | 6870 | 53,000 | 178,000 |
SD | 1310 | 11,100 | 41,600 |
AUCinf (h∗μg/mL) | |||
Mean | 7010 | 55,900 | 218,000 |
SD | 1650 | 13,400 | 81,700 |
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Xu, X.; Yan, S.-L.; Yo, Y.-T.; Chiang, P.; Tsai, C.-Y.; Lin, L.-L.; Qin, A. A Novel Monoclonal Antibody against PD-1 for the Treatment of Viral Oncogene-Induced Tumors or Other Cancer. Cancers 2024, 16, 3052. https://doi.org/10.3390/cancers16173052
Xu X, Yan S-L, Yo Y-T, Chiang P, Tsai C-Y, Lin L-L, Qin A. A Novel Monoclonal Antibody against PD-1 for the Treatment of Viral Oncogene-Induced Tumors or Other Cancer. Cancers. 2024; 16(17):3052. https://doi.org/10.3390/cancers16173052
Chicago/Turabian StyleXu, Xu, Shih-Long Yan, Yi-Te Yo, Peiyu Chiang, Chan-Yen Tsai, Lih-Ling Lin, and Albert Qin. 2024. "A Novel Monoclonal Antibody against PD-1 for the Treatment of Viral Oncogene-Induced Tumors or Other Cancer" Cancers 16, no. 17: 3052. https://doi.org/10.3390/cancers16173052