| 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
|
| Project Status |
Completed (Fiscal Year 2017)
|
| Budget Amount *help |
¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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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 / がん / PD-1 / 免疫治療 |
|---|
| 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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