Preclinical Characterization of Efficacy and Pharmacodynamic Properties of Finotonlimab, a Humanized Anti-PD-1 Monoclonal Antibody
Abstract
:1. Introduction
2. Results
2.1. High Affinity and Binding Specificity of Finotonlimab to hPD-1
2.2. Epitope of Finotonlimab Overlaps with PD-L1/PD-L2 Binding Sites
2.3. In Vitro Effects on the Function of T Cell Activation by Finotonlimab
2.4. Finotonlimab Exhibited Antitumor Activity in Mouse Xenograft Models
2.5. Fc-Mediated Effector Functions of Finotonlimab
2.6. Comparative Pharmacokinetics of Finotonlimab and Anti-PD-1 Antibodies in Cynomolgus Monkeys
2.7. Pharmacokinetic and Pharmacodynamic Profiles of Finotonlimab in Cynomolgus Monkeys Following Single and Repeated Administrations
2.8. Toxicology Evaluation Following Repeated Administrations of Finotonlimab in Cynomolgus Monkeys
3. Discussion
4. Materials and Methods
4.1. Reagents
4.2. Animals
4.3. Affinity Measurements by Octet
4.4. Epitope Mapping of PD-L1/PD-L2 and Finotonlimab Binding
4.5. Structural Modeling of Finotonlimab/PD-1 Complex and Epitope Analysis
4.6. Binding Affinity of Finotonlimab by ELISA
4.7. Blocking Capability of Finotonlimab by ELISA
4.8. Binding of the Finotonlimab to PD-1 Cell Surfaces by FACS
4.9. Evaluating Human PD-1/PD-L1 Blocking Capability of Finotonlimab by FACS
4.10. T Cell Activation Assay-Associated Luciferase Reporter System
4.11. In Vitro Mixed Lymphocyte Reaction
4.12. ADCC/ADCP-Activation Assays
4.13. CDC Cytotoxicity Assay
4.14. MC38 Tumor Mouse Models
4.15. B16F1 Tumor Mouse Models
4.16. hPBMC-Reconstituted A431 Mouse Models
4.17. Pharmacokinetic and Toxicity Assessments of Finotonlimab in Cynomolgus Monkeys
4.18. Anesthesia and Euthanasia
4.19. Receptor Occupancy Assay
4.20. Statistical Analysis
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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KD (M) | Kon (M−1s−1) | Kdis (s−1) | |
---|---|---|---|
7.13 × 10−11 | 2.95 × 105 | 2.10 × 10−5 | |
Finotonlimab | 5.46 × 10−11 | 3.06 × 105 | 1.67 × 10−5 |
6.84 × 10−11 | 3.03 × 105 | 2.07 × 10−5 | |
Mean | 6.48 × 10−11 | 3.01 × 105 | 1.95 × 10−5 |
6.80 × 10−11 | 6.89 × 105 | 4.68 × 10−5 | |
Nivolumab | 7.92 × 10−11 | 7.02 × 105 | 5.56 × 10−5 |
7.50 × 10−11 | 6.84 × 105 | 5.13 × 10−5 | |
Mean | 7.41 × 10−11 | 6.92 × 105 | 5.12 × 10−5 |
Dose (mg/kg) | Gender | / | T1/2 h | Cmax μg/mL | AUClast h·mg/mL | AUCinf h·mg/mL | MRT h | Cmax Ratio | AUC Ratio |
---|---|---|---|---|---|---|---|---|---|
1 | M | Mean | 178.34 | 30.13 | 2.71 | 4.46 | 92.09 | 1.00 | 1.00 |
SD | 45.79 | 2.59 | 0.37 | 1.25 | 6.06 | ||||
F | Mean | 128.50 | 25.02 | 3.44 | 3.87 | 136.68 | 1.00 | 1.00 | |
SD | 25.43 | 9.95 | 0.85 | 0.91 | 25.12 | ||||
3 | M | Mean | 169.15 | 84.58 | 10.89 | 14.40 | 132.52 | 2.81 | 4.02 |
SD | 26.36 | 7.20 | 2.30 | 1.58 | 34.03 | ||||
F | Mean | 202.20 | 84.28 | 12.53 | 14.23 | 194.32 | 3.37 | 3.64 | |
SD | 41.68 | 5.71 | 1.23 | 2.47 | 6.66 | ||||
10 | M | Mean | 191.71 | 339.39 | 44.22 | 61.49 | 151.24 | 11.26 | 16.33 |
SD | 44.67 | 33.15 | 10.76 | 5.38 | 62.38 | ||||
F | Mean | 215.62 | 299.93 | 49.72 | 60.24 | 217.85 | 11.99 | 14.45 | |
SD | 154.11 | 27.57 | 10.02 | 20.85 | 48.02 |
Receptor Occupation | 1 mg/kg | 3 mg/kg | 10 mg/kg | |||
---|---|---|---|---|---|---|
Time for Blood Collection | Mean (%) | SD (%) | Mean (%) | SD (%) | Mean (%) | SD (%) |
Before dose | 8.65 | 2.03 | 8.94 | 2.46 | 9.67 | 4.76 |
2 h | 89.52 | 6.60 | 93.90 | 3.11 | 95.35 | 8.51 |
24 h | 88.47 | 4.38 | 87.98 | 3.87 | 93.17 | 2.61 |
72 h | 93.33 | 2.79 | 93.52 | 9.54 | 100.36 | 5.07 |
168 h | 92.09 | 5.44 | 87.68 | 4.65 | 93.69 | 4.63 |
336 h | 59.00 | 40.16 | 76.51 | 22.26 | 89.80 | 19.64 |
504 h | 33.68 | 41.48 | 68.09 | 47.21 | 70.91 | 33.26 |
672 h | 10.43 | 4.32 | 41.26 | 39.19 | 50.00 | 43.11 |
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Yao, Y.; Yang, X.; Li, J.; Guo, E.; Wang, H.; Sun, C.; Hong, Z.; Zhang, X.; Jia, J.; Wang, R.; et al. Preclinical Characterization of Efficacy and Pharmacodynamic Properties of Finotonlimab, a Humanized Anti-PD-1 Monoclonal Antibody. Pharmaceuticals 2025, 18, 395. https://doi.org/10.3390/ph18030395
Yao Y, Yang X, Li J, Guo E, Wang H, Sun C, Hong Z, Zhang X, Jia J, Wang R, et al. Preclinical Characterization of Efficacy and Pharmacodynamic Properties of Finotonlimab, a Humanized Anti-PD-1 Monoclonal Antibody. Pharmaceuticals. 2025; 18(3):395. https://doi.org/10.3390/ph18030395
Chicago/Turabian StyleYao, Yunqi, Xiaoning Yang, Jing Li, Erhong Guo, Huiyu Wang, Chunyun Sun, Zhangyong Hong, Xiao Zhang, Jilei Jia, Rui Wang, and et al. 2025. "Preclinical Characterization of Efficacy and Pharmacodynamic Properties of Finotonlimab, a Humanized Anti-PD-1 Monoclonal Antibody" Pharmaceuticals 18, no. 3: 395. https://doi.org/10.3390/ph18030395
APA StyleYao, Y., Yang, X., Li, J., Guo, E., Wang, H., Sun, C., Hong, Z., Zhang, X., Jia, J., Wang, R., Ma, J., Dai, Y., Deng, M., Yu, C., Sun, L., & Xie, L. (2025). Preclinical Characterization of Efficacy and Pharmacodynamic Properties of Finotonlimab, a Humanized Anti-PD-1 Monoclonal Antibody. Pharmaceuticals, 18(3), 395. https://doi.org/10.3390/ph18030395