Vaccination using peptides spanning the SYT–SSX tumor-specific translocation

Abstract

Evaluation of: Kawaguchi S, Tsukahara T, Ida K et al. SYT–SSX breakpoint peptide vaccines in patients with synovial sarcoma: a study from the Japanese Musculoskeletal Oncology Group. Cancer Sci. 103(9), 1625–1630 (2012).The identification of genetic translocations as key tumor-initiating events has led to the development of novel antigen-specific vaccines targeting these tumor-specific breakpoint regions. Previous studies have evaluated vaccines targeting the breakpoints in the BCR-ABL translocation in patients with chronic myelogenous leukemia and EWS-FLI1 in patients with Ewing sarcoma. In the article under evaluation, the authors evaluated a peptide vaccine targeting the breakpoint in the SYT–SSX translocation, the genetic translocation essentially pathognomonic for synovial sarcoma. This is the second small clinical trial reported by this group using HLA-A24-binding peptides as vaccine antigens. In this four-arm trial, using a native or HLA-A24-optimized SYT–SSX peptide with or without adjuvant plus IFN-α, they immunized patients with metastatic synovial sarcoma. Immune responses were evaluated by delayed-type hypersensitivity testing and tetramer analysis. No robust evidence of immune response to the target epitope was detected. Some patients treated with peptide in adjuvant plus IFN-α had stable disease. These results suggest that future similar studies might best evaluate patients with a lower burden of disease, consider alternative immunization approaches to the SYT–SSX target antigen and consider the efficacy of IFN-α alone for the treatment of synovial sarcoma.