Preclinical Pharmacokinetics and Pharmacology Study of RC98 : A Programmed Cell Death Ligand 1 Monoclonal Antibody in Cynomolgus Monkeys
Copyright© Bentham Science Publishers; For any queries, please email at epubbenthamscience.net..
INTRODUCTION: RC98 is the monoclonal antibody against Programmed Cell Death Ligand 1 (PD-L1). Relevant reports have confirmed that the influence of PD-L1 expressed by tumor cells on antitumor CD8+ T cell responses is well characterized, but the impact of PD-L1 expressed by immune cells has not been well defined.
OBJECTIVE: This study aimed to design a Pharmacokinetics/Pharmacology (PK/PD) study of RC98 in normal cynomolgus monkeys to research the effect on the immune system.
METHODS: RC98 and vehicle were administered to cynomolgus monkeys at 15 mg/kg via intravenous infusion once a week for 4 weeks to evaluate the relationship between PK and PD. The pharmacodynamic activity was measured by the PD-L1 receptor occupancy (RO) in CD3+ T cells, A T-cell-dependent antibody response (TDAR), and the concentration of soluble PD-L1.
RESULTS: The pharmacokinetic result showed that the exposure from the last administration was lower than that of the first administration, probably due to immunogenicity production. There was a strong correlation between systemic exposure and RO in CD3+ T cells but decreased RO levels after the last dose, which indirectly reflected the activation of T cells. The keyhole limpet hemocyanin (KLH)-induced TDAR in the RC98 group was higher than in the vehicle group. The concentration of soluble PD-L1 had increased feedback with RC98, and the concentration of soluble PD-L1 was maintained at a higher level after multiple doses than before dosing.
CONCLUSION: These data indicate that the immune system was clearly activated. In addition, the non-clinical data could provide a basis for its efficacy evaluation in clinical trials.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - year:2024 |
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| Enthalten in: |
Current pharmaceutical design - (2024) vom: 15. Apr. |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Wang, Ling [VerfasserIn] |
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| Links: |
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| Themen: |
Journal Article |
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| Anmerkungen: |
Date Revised 16.04.2024 published: Print-Electronic Citation Status Publisher |
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| doi: |
10.2174/0113816128248929230920071937 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM371130948 |
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| 245 | 1 | 0 | |a Preclinical Pharmacokinetics and Pharmacology Study of RC98 |b A Programmed Cell Death Ligand 1 Monoclonal Antibody in Cynomolgus Monkeys |
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| 500 | |a Date Revised 16.04.2024 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status Publisher | ||
| 520 | |a Copyright© Bentham Science Publishers; For any queries, please email at epubbenthamscience.net. | ||
| 520 | |a INTRODUCTION: RC98 is the monoclonal antibody against Programmed Cell Death Ligand 1 (PD-L1). Relevant reports have confirmed that the influence of PD-L1 expressed by tumor cells on antitumor CD8+ T cell responses is well characterized, but the impact of PD-L1 expressed by immune cells has not been well defined | ||
| 520 | |a OBJECTIVE: This study aimed to design a Pharmacokinetics/Pharmacology (PK/PD) study of RC98 in normal cynomolgus monkeys to research the effect on the immune system | ||
| 520 | |a METHODS: RC98 and vehicle were administered to cynomolgus monkeys at 15 mg/kg via intravenous infusion once a week for 4 weeks to evaluate the relationship between PK and PD. The pharmacodynamic activity was measured by the PD-L1 receptor occupancy (RO) in CD3+ T cells, A T-cell-dependent antibody response (TDAR), and the concentration of soluble PD-L1 | ||
| 520 | |a RESULTS: The pharmacokinetic result showed that the exposure from the last administration was lower than that of the first administration, probably due to immunogenicity production. There was a strong correlation between systemic exposure and RO in CD3+ T cells but decreased RO levels after the last dose, which indirectly reflected the activation of T cells. The keyhole limpet hemocyanin (KLH)-induced TDAR in the RC98 group was higher than in the vehicle group. The concentration of soluble PD-L1 had increased feedback with RC98, and the concentration of soluble PD-L1 was maintained at a higher level after multiple doses than before dosing | ||
| 520 | |a CONCLUSION: These data indicate that the immune system was clearly activated. In addition, the non-clinical data could provide a basis for its efficacy evaluation in clinical trials | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a RC98 | |
| 650 | 4 | |a T cell-dependent antibody response | |
| 650 | 4 | |a pharmacokinetic | |
| 650 | 4 | |a receptor occupancy | |
| 650 | 4 | |a soluble PD-L1 | |
| 700 | 1 | |a Li, Qiaoning |e verfasserin |4 aut | |
| 700 | 1 | |a Deng, Chenglian |e verfasserin |4 aut | |
| 700 | 1 | |a Liu, Zhihao |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Fang |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Shenjun |e verfasserin |4 aut | |
| 700 | 1 | |a Dong, Lihou |e verfasserin |4 aut | |
| 700 | 1 | |a Jiang, Jing |e verfasserin |4 aut | |
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