2017 Fiscal Year Final Research Report
Evaluation of Pharmacokinetic and efficacy of Anti-PD-1/PD-L1 Antibodies and development of PBPK models.
| Project/Area Number |
16H06671
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| Research Category |
Grant-in-Aid for Research Activity Start-up
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| Allocation Type | Single-year Grants |
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| Research Field |
Medical pharmacy
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| Research Institution | Chiba University |
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Principal Investigator |
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| Project Period (FY) |
2016-08-26 – 2018-03-31
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| Keywords | 免疫チェックポイント阻害剤 / 抗体医薬 / 薬物動態学 |
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| Outline of Final Research Achievements |
Recently anti-PD-1 antibodies (aPD-1 Abs), anti-PD-L1 (aPD-1) Abs have been approved. However, the difference between both Abs in pharmacokinetics and anti-tumor effects have not been fully understood. In this study, we analyzed the difference between both Abs in blood concentration, biodistribution and degradation in tumor-bearing mice by using aPD-1/PD-L1 Abs labeled with radioisotopes (111In) and evaluated the relationship between PK and therapeutic effects. It was observed that aPD-L1 Abs were largely accumulated in normal tissues, especially in the spleen and liver and degraded rapidly compared with aPD-1 Abs, resulting that the blood concentration and distribution in tumors of aPD-L1 Abs tended to be low. the PK of aPD-1/PD-L1 Abs which target the same axis were not equivalent and the selectivity of expression of target molecules in both normal tissues and tumors should be considered to optimize their therapeutic efficacy. We attempted to develop PBPK models by obtained PK data.
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| Free Research Field |
がん免疫治療
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