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 (90Y)‐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 90Y‐MAb 92‐13 and 9 days for mice treated with non‐labeled antibody control or untreated mice (difference = 49 days; P = 7 × 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. (Cancer Sci 2008; 99: 432–440)