| Project/Area Number |
20790377
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
Immunology
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| Research Institution | Kagoshima University |
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Principal Investigator |
NAGAI Taku Kagoshima University, 大学院・医歯学総合研究科, 助教 (90363647)
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| Project Period (FY) |
2008 – 2009
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| Project Status |
Completed (Fiscal Year 2009)
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| Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2009: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Fiscal Year 2008: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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| Keywords | マクロファージ / がん / 葉酸受容体β / 炎症 / 抗体医薬 / 低分子高機能型抗体 / イムノトキシン / 癌 / 抗体製剤 / 前臨床試験 |
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| Research Abstract |
Recently, clinical and experimental evidence suggested that inflammatory macrophages, such as tumor-associated macrophages (TAMs) play important role in malignant tumors. We have shown that synovial macrophages in rheumatoid arthritis express folate receptor β (FRβ) while tissue resident macrophages in normal tissues and peripheral blood monocytes express no or low levels of FRβ. We tested whether TAMs express FRβ in human malignant tumors and nude mice xenograft model and if so, whether selectively elimination of FRβ-expressing TAMs could suppress tumor growth in nude mice model.
Our results showed the following novel features of FRβ-expressing TAMs : (a) immunohistochemical analysis revealed that FRβ-expressing TAMs were present in glioblastoma, lung cancer, and pancreatic cancer; (b) also, FRβ-expressing TAMs were present in nude mice implanted with rat C6 glioma model; (c) injection of the anti-FRβ immunotoxin (consisting of heavy and light chain Fv portions and Pseudomonas exotoxin A) into C6 glioma xenografts in nude mice significantly depleted TAMs and reduced tumor growth and CD31-positive vascular area; (d) immunotoxin inhibited NO and VEGF production by FRβ-expressing macrophages in vitro.
Our study indicated that FRβ-expressing TAMs may promote tumor growth in glioblastoma, and suggested that targeting FRβ-expressing macrophages could be an effective anti-cancer therapy method.
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