Background. Patients with recurrent synovial sarcomas have few options for systemic therapy. Since they express large amounts of endogenous CT (cancer testis) antigens such as NY-ESO-1, we investigated the clinical activity of single agent anti-CTLA4 antibody ipilimumab in patients with advanced or metastatic synovial sarcoma. Methods. A Simon two-stage phase II design was used to determine if there was sufficient activity to pursue further. The primary endpoint was tumor response rate by RECIST 1.0. Patients were treated with ipilimumab 3？mg/kg intravenously every 3 weeks for three cycles and then restaged. Retreatment was possible for patients receiving an extra three-week break from therapy. Sera and peripheral blood mononuclear cells were collected before and during therapy to assess NY-ESO-1-specific immunity. Results. Six patients were enrolled and received 1–3 cycles of ipilimumab. All patients showed clinical or radiological evidence of disease progression after no more than three cycles of therapy, for a RECIST response rate of 0%. The study was stopped for slow accrual, lack of activity, and lack of immune response. There was no evidence of clinically significant either serologic or delayed type hypersensitivity responses to NY-ESO-1 before or after therapy. Conclusion. Despite high expression of CT antigens by synovial sarcomas of patients treated in this study, there was neither clinical benefit nor evidence of anti-CT antigen serological responses. Assessment of the ability of synovial sarcoma cell lines to present cancer-germ cell antigens may be useful in determining the reason for the observed lack of immunological or clinical activity. 1. Introduction Synovial sarcoma (SS) is one of the more common forms of soft tissue sarcoma, with an incidence of approximately 3 per million [1]. It presents as a painless or painful mass, typically in an extremity, with a peak incidence around adolescence and young adulthood [2]. SS is characterized genetically by a t(X;18) translocation involving SS18 and either SSX1, SSX2, or SSX4 [3–8]. While surgery and radiation therapy are usually effective in controlling local disease [9], approximately 40% of patients with synovial sarcoma will die of metastatic disease [10]. Chemotherapies including ifosfamide, doxorubicin, and possibly trabectedin have demonstrated activity against SS; however, responses are not durable [11–14]. As a result, the development of novel therapies remains a focus of research for this diagnosis. One area of focus has centered on the finding that the SS18-SSX translocation product
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