Radioimmunotherapy of human synovial sarcoma using a monoclonal antibody against FZD10.
We previously reported Frizzled homolog 10 (FZD10), a member of the Frizzled family, to be a promising therapeutic target for synovial sarcomas. In this report, we established a murine monoclonal antibody (MAb), namely, MAb 92-13 that had specific binding activity against native FZD10 product expressed in synovial sarcoma cell lines. Subsequent immunohistochemical analyses with the MAb 92-13 confirmed an absence or hardly detectable level of FZD10 protein in any normal human organs. We confirmed the specific binding activity of this MAb in vivo after injection of fluorescent-labeled MAb i.p. or i.v. into the mice carrying synovial sarcoma xenografts by the use of the in vivo fluorescent imaging system as well as radioisotopes. Moreover, MAb 92-13 was effectively internalized into the synovial sarcoma cells after its binding to FZD10 on the cell surface. A single i.v. injection of the Yttrium-90 ((90)Y)-MAb 92-13 drastically suppressed tumor growth of synovial sarcoma in mice without any severe toxicity. Median time to tumor progression was 58 days for mice treated with (90)Y-MAb 92-13 and 9 days for mice treated with non-labeled antibody control or untreated mice (difference = 49 days; P = 7 x 10(-5)). This result indicates that MAb 92-13 could be utilized as the novel treatment modality for synovial sarcoma and other FZD10-positive tumors.
Fukukawa
Chikako
C
Laboratory of Molecular Medicine, Human Genome Center, Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan.
Hanaoka
Hirofumi
H
Nagayama
Satoshi
S
Tsunoda
Tatsuhiko
T
Toguchida
Junya
J
Endo
Keigo
K
Nakamura
Yusuke
Y
Katagiri
Toyomasa
T
D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000276:immunology / Q000627:therapeutic use*; D019556:COS Cells; D045744:Cell Line, Tumor; D002522:Chlorocebus aethiops; D051157:Frizzled Receptors / Q000037:antagonists & inhibitors* / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D051379:Mice; D018613:Microscopy, Confocal; D023421:Models, Animal; D016499:Radioimmunotherapy; D043562:Receptors, G-Protein-Coupled / Q000037:antagonists & inhibitors* / Q000276:immunology / Q000378:metabolism; D013584:Sarcoma, Synovial / Q000276:immunology / Q000532:radiotherapy*
D000911:Antibodies, Monoclonal; C121168:FZD10 protein, human; D051157:Frizzled Receptors; D043562:Receptors, G-Protein-Coupled