title: SSX antigens as tumor vaccine targets in human sarcoma.
abstract: The efficacy of current standard therapies for the treatment of sarcoma remains limited. With the aim of identifying target antigens relevant to the development of vaccine-based immunotherapy of sarcoma, we have addressed the relevance of tumor-specific antigens encoded by genes belonging to the SSX family as vaccine targets in sarcoma tumors. Expression of SSX-1 to -5 was analyzed in a collection of sarcoma tumors of diverse histological subtypes and in sarcoma cell lines. We found expression of at least one SSX-encoded antigen in 42% of sarcoma tumors, including 5 of 7 different histological subtypes, and in 50% of sarcoma cell lines. SSX-1 was the most frequently expressed family member, followed by SSX-4, -2 and -5. Expression of SSX-3 was detected in only one sample. Importantly, most SSX positive samples co-expressed more than one family member. In addition, assessment of CD8+ T cell recognition of HLA-A2+ SSX-2+ sarcoma cells showed that the latter were efficiently recognized and lysed by SSX-2-specific CTLs. The results of this study indicate that SSX antigens are relevant targets for the development of vaccine-based immunotherapy of sarcoma and encourage the start of vaccination trials using SSX-derived immunogens in sarcoma patients.
authors.affiliation: Ludwig Institute Clinical Trial Center, Division of Medical Oncology, Department of Medicine, Columbia University College of Physicians and Surgeons, New York, NY 10032, USA.
authors.forename: Maha
authors.initials: M
authors.lastname: Ayyoub
authors.forename: Michelle
authors.initials: M
authors.lastname: Brehm
authors.forename: Geneviève
authors.initials: G
authors.lastname: Metthez
authors.forename: Susan
authors.initials: S
authors.lastname: Talbot
authors.forename: Valerie
authors.initials: V
authors.lastname: Dutoit
authors.forename: Robert N
authors.initials: RN
authors.lastname: Taub
authors.forename: Mary-Louise
authors.initials: ML
authors.lastname: Keohan
authors.forename: Ali O
authors.initials: AO
authors.lastname: Gure
authors.forename: Yao-Tseng
authors.initials: YT
authors.lastname: Chen
authors.forename: Barbara
authors.initials: B
authors.lastname: Williamson
authors.forename: Achim A
authors.initials: AA
authors.lastname: Jungbluth
authors.forename: Lloyd J
authors.initials: LJ
authors.lastname: Old
authors.forename: Charles S
authors.initials: CS
authors.lastname: Hesdorffer
authors.forename: Danila
authors.initials: D
authors.lastname: Valmori
mesh_terms: D000951:Antigens, Neoplasm / Q000627:therapeutic use*; D019496:Cancer Vaccines / Q000627:therapeutic use*; D006801:Humans; D009363:Neoplasm Proteins / Q000627:therapeutic use*; D012097:Repressor Proteins / Q000627:therapeutic use*; D012509:Sarcoma / Q000276:immunology* / Q000473:pathology; D014407:Tumor Cells, Cultured; D014614:Vaccines, Synthetic / Q000627:therapeutic use
chemical_list: D000951:Antigens, Neoplasm; D019496:Cancer Vaccines; D009363:Neoplasm Proteins; D012097:Repressor Proteins; D014614:Vaccines, Synthetic; C093962:synovial sarcoma X breakpoint proteins