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

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.

• Authors: Taku Nagai, Masashi Tanaka, Yasuhiro Tsuneyoshi, Baohui Xu, Sara A Michie, Kazuhisa Hasui, Hirofumi Hirano, Kazunori Arita, Takami Matsuyama
• Journal: Cancer immunology, immunotherapy : CII (Cancer Immunol Immunother) Vol. 58 Issue 10 Pg. 1577-86 (Oct 2009) ISSN: 1432-0851 [Electronic] Germany
• PMID: 19238383 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antibodies, Monoclonal
• Bacterial Toxins
• Carrier Proteins
• Exotoxins
• Folate Receptors, GPI-Anchored
• Immunoglobulin Variable Region
• Immunotoxins
• Receptors, Cell Surface
• Recombinant Fusion Proteins
• Vascular Endothelial Growth Factor A
• Virulence Factors
• vascular endothelial growth factor A, mouse
• Nitric Oxide
• ADP Ribose Transferases
• Pseudomonas aeruginosa exotoxin A

Topics

• ADP Ribose Transferases (therapeutic use)
• Animals
• Antibodies, Monoclonal (immunology)
• Antibody-Dependent Cell Cytotoxicity
• Bacterial Toxins (therapeutic use)
• Carrier Proteins (immunology)
• Exotoxins (therapeutic use)
• Female
• Folate Receptors, GPI-Anchored
• Glioblastoma (immunology, pathology, therapy)
• Immunoenzyme Techniques
• Immunoglobulin Variable Region (immunology)
• Immunotoxins (therapeutic use)
• Macrophages, Peritoneal (immunology)
• Mastocytoma (immunology, therapy)
• Mice
• Mice, Inbred BALB C
• Mice, Nude
• Multiple Myeloma (immunology, therapy)
• Nitric Oxide (metabolism)
• Rats
• Receptors, Cell Surface (immunology)
• Recombinant Fusion Proteins (therapeutic use)
• Survival Rate
• Vascular Endothelial Growth Factor A (metabolism)
• Virulence Factors (therapeutic use)
• Xenograft Model Antitumor Assays