دورية أكاديمية
Preclinical Characterization of a Novel Anti-Cancer PD-L1 Inhibitor RPH-120
| العنوان: | Preclinical Characterization of a Novel Anti-Cancer PD-L1 Inhibitor RPH-120 |
|---|---|
| المؤلفون: | Andrey Kulikov, Elena Shipaeva, Anastasia Dmitrieva, Vera Batrak, Georgy Shipunov, Colin Guy, Jill Smith, Ran Zhang, Michael Zhang, Jeff Duan, Anton Chestukhin, Sergei Barbashov, Mikhail Samsonov, Yan Lavrovsky |
| المصدر: | Frontiers in Pharmacology, Vol 12 (2021) |
| بيانات النشر: | Frontiers Media S.A., 2021. |
| سنة النشر: | 2021 |
| المجموعة: | LCC:Therapeutics. Pharmacology |
| مصطلحات موضوعية: | cancer immunotherapy, monoclonal antibody, PD-L1, in vitro efficacy, animal models, therapeutic agent, Therapeutics. Pharmacology, RM1-950 |
| الوصف: | RPH-120 is a novel fully human anti-PD-L1 IgG1 monoclonal antibody with specifically designed Asn300Ala mutation in Fc fragment. Surface plasmon resonance assay showed that affinity of the RPH-120 to the dimeric form of human PD-L1-Fc fusion protein was much higher than affinity to the monomeric His-tagged PD-L1. Further binding studies demonstrated that RPH-120 is able to bind to human and monkey but not mouse PD-L1. Tissue cross-reactivity study showed good comparability of human and Cynomolgus monkeys tissue staining. Bioactivity was assessed using mixed lymphocyte reaction assay. This study revealed that RPH-120 was able to activate T cells preventing PD1/PD-L1 interaction. Antitumor efficacy was analyzed in HCC-827 lung cancer xenografts in humanized CD34+ mice at three dosage levels: 20, 80, and 200 mg/kg. RPH-120 demonstrated significant tumor growth inhibition, and this inhibition was comparable to that of atezolizumab. In a single dose toxicity, toxicokinetic and dose range finding study performed in Cynomolgus monkeys, RPH-120 was administered via intravenous (IV) bolus or 60-min IV infusion, followed by 8-weeks recovery period. An acceptable toxicokinetic profile was demonstrated and administration at doses of up to 200 mg/kg was well tolerated by all animals. In conclusion, RPH-120 revealed promising in vitro and in vivo activity and safety. RPH-120 is a potent anti-PD-L1 drug candidate for cancer immunotherapy. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 1663-9812 |
| العلاقة: | https://www.frontiersin.org/articles/10.3389/fphar.2021.723038/fullTest; https://doaj.org/toc/1663-9812Test |
| DOI: | 10.3389/fphar.2021.723038 |
| الوصول الحر: | https://doaj.org/article/5dbb2234d8f24276a1a0965cf6215e2eTest |
| رقم الانضمام: | edsdoj.5dbb2234d8f24276a1a0965cf6215e2e |
| قاعدة البيانات: | Directory of Open Access Journals |
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