Targeting tumor-associated macrophages in an experimental glioma model with a recombinant immunotoxin to folate receptor beta.
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.
Nagai
Taku
T
Department of Immunology, Graduate School of Medical and Dental Sciences, Kagoshima University, 8-35-1 Sakuragaoka, Kagoshima, 890-8544, Japan.
Tanaka
Masashi
M
Tsuneyoshi
Yasuhiro
Y
Xu
Baohui
B
Michie
Sara A
SA
Hasui
Kazuhisa
K
Hirano
Hirofumi
H
Arita
Kazunori
K
Matsuyama
Takami
T
D036002:ADP Ribose Transferases / Q000627:therapeutic use*; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D000920:Antibody-Dependent Cell Cytotoxicity; D001427:Bacterial Toxins / Q000627:therapeutic use*; D002352:Carrier Proteins / Q000276:immunology*; D005098:Exotoxins / Q000627:therapeutic use*; D005260:Female; D058973:Folate Receptors, GPI-Anchored; D005909:Glioblastoma / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D007124:Immunoenzyme Techniques; D007135:Immunoglobulin Variable Region / Q000276:immunology; D000922:Immunotoxins / Q000627:therapeutic use*; D017737:Macrophages, Peritoneal / Q000276:immunology*; D034801:Mastocytoma / Q000276:immunology / Q000628:therapy; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009101:Multiple Myeloma / Q000276:immunology / Q000628:therapy; D009569:Nitric Oxide / Q000378:metabolism; D051381:Rats; D011956:Receptors, Cell Surface / Q000276:immunology*; D011993:Recombinant Fusion Proteins / Q000627:therapeutic use*; D015996:Survival Rate; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D037521:Virulence Factors / Q000627:therapeutic use*; D023041:Xenograft Model Antitumor Assays; D000097668:Pseudomonas aeruginosa Exotoxin A
D036002:ADP Ribose Transferases; D000911:Antibodies, Monoclonal; D001427:Bacterial Toxins; D002352:Carrier Proteins; D005098:Exotoxins; D058973:Folate Receptors, GPI-Anchored; D007135:Immunoglobulin Variable Region; D000922:Immunotoxins; D009569:Nitric Oxide; D011956:Receptors, Cell Surface; D011993:Recombinant Fusion Proteins; D042461:Vascular Endothelial Growth Factor A; D037521:Virulence Factors; D000097668:Pseudomonas aeruginosa Exotoxin A; C467480:vascular endothelial growth factor A, mouse