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

利用重组免疫毒素靶向叶酸受体 β,靶向实验性胶质瘤模型中的肿瘤相关巨噬细胞

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作者:Taku Nagai, Masashi Tanaka, Yasuhiro Tsuneyoshi, Baohui Xu, Sara A Michie, Kazuhisa Hasui, Hirofumi Hirano, Kazunori Arita, Takami Matsuyama

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 beta (FR beta) was expressed on macrophages in human glioblastomas and a rat C6 glioma implanted subcutaneously in nude mice. To target FR beta-expressing TAMs, we produced a recombinant immunotoxin consisting of immunoglobulin heavy and light chain Fv portions of an anti-mouse FR beta 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 FR beta-expressing macrophages will provide a therapeutic tool for human glioblastomas.

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