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Targeting tumor-associated macrophages in an experimental glioma model with a recombinant immunotoxin to folate receptor β

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Abstract

Tumor-associated macrophages (TAMs) are frequently found in glioblastomas and a high degree of macrophage infiltration is associated with a poor prognosis for glioblastoma patients. However, it is unclear whether TAMs in glioblastomas promote tumor growth. In this study, we found that folate receptor β (FRβ) was expressed on macrophages in human glioblastomas and a rat C6 glioma implanted subcutaneously in nude mice. To target FRβ-expressing TAMs, we produced a recombinant immunotoxin consisting of immunoglobulin heavy and light chain Fv portions of an anti-mouse FRβ monoclonal antibody and Pseudomonas exotoxin A. Injection of the immunotoxin into C6 glioma xenografts in nude mice significantly depleted TAMs and reduced tumor growth. The immunotoxin targeting FRβ-expressing macrophages will provide a therapeutic tool for human glioblastomas.

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Acknowledgments

This work was supported by KAKENHI (20790377), a Grant-in-Aid for Young Scientists (B) from the Ministry of Education, Culture, Sports, Science and Technology (MEXT) of Japan, and the Kodama Memorial Fund Medical Research.

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Authors and Affiliations

  1. Department of Immunology, Graduate School of Medical and Dental Sciences, Kagoshima University, 8-35-1 Sakuragaoka, Kagoshima, 890-8544, Japan

    Taku Nagai, Masashi Tanaka, Yasuhiro Tsuneyoshi, Kazuhisa Hasui & Takami Matsuyama

  2. Department of Pathology, Stanford University School of Medicine, Stanford, USA

    Baohui Xu & Sara A. Michie

  3. Department of Neurosurgery, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan

    Hirofumi Hirano & Kazunori Arita

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  1. Taku Nagai
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  2. Masashi Tanaka
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  3. Yasuhiro Tsuneyoshi
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  4. Baohui Xu
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  5. Sara A. Michie
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  6. Kazuhisa Hasui
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  7. Hirofumi Hirano
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  8. Kazunori Arita
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  9. Takami Matsuyama
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Correspondence to Takami Matsuyama.

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Nagai, T., Tanaka, M., Tsuneyoshi, Y. et al. Targeting tumor-associated macrophages in an experimental glioma model with a recombinant immunotoxin to folate receptor β. Cancer Immunol Immunother 58, 1577–1586 (2009). https://doi.org/10.1007/s00262-009-0667-x

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  • DOI: https://doi.org/10.1007/s00262-009-0667-x

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