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Updated: Jun 25, 2026
Coculture Assays to Study Macrophage and Microglia Stimulation of Glioblastoma Invasion
Published on: October 20, 2016
Targeting tumor-associated macrophages in an experimental glioma model with a recombinant immunotoxin to folate
Taku Nagai1, Masashi Tanaka, Yasuhiro Tsuneyoshi
1Department of Immunology, Graduate School of Medical and Dental Sciences, Kagoshima University, 8-35-1 Sakuragaoka, Kagoshima, 890-8544, Japan.
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.
Insights
Targeting folate receptor beta (FR beta)-expressing tumor-associated macrophages (TAMs) in glioblastomas with a novel immunotoxin effectively reduced tumor growth in preclinical models. This approach offers a potential new therapy for glioblastoma. Keywords: glioblastoma, tumor-associated macrophages, folate receptor beta, immunotoxin, tumor growth.
Area of Science:
- Oncology
- Immunology
- Molecular Biology
Background:
- Tumor-associated macrophages (TAMs) infiltrate glioblastomas, correlating with poor patient prognosis.
- The role of TAMs in promoting glioblastoma growth remains unclear.
- Folate receptor beta (FR beta) is identified on macrophages within glioblastomas.
Purpose of the Study:
- To investigate the expression of FR beta on TAMs in glioblastomas.
- To develop and evaluate a targeted immunotoxin for FR beta-expressing TAMs.
- To assess the therapeutic potential of targeting TAMs in glioblastoma models.
Main Methods:
- Expression analysis of FR beta on macrophages in human glioblastomas and rat C6 glioma xenografts.
- Production of a recombinant immunotoxin targeting mouse FR beta using Pseudomonas exotoxin A.
- Administration of the immunotoxin into C6 glioma xenografts in nude mice to assess TAM depletion and tumor growth inhibition.
Main Results:
- FR beta was found to be expressed on macrophages in human glioblastomas and C6 glioma xenografts.
- The anti-FR beta immunotoxin significantly depleted TAMs in C6 glioma xenografts.
- Treatment with the immunotoxin resulted in reduced tumor growth in the xenograft model.
Conclusions:
- FR beta is a viable target on TAMs in glioblastoma.
- Targeting FR beta-expressing TAMs with a recombinant immunotoxin demonstrates therapeutic efficacy in preclinical models.
- This immunotoxin represents a promising therapeutic strategy for human glioblastomas.
