SSX antigens as tumor vaccine targets in human sarcoma.
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.
Ayyoub
Maha
M
Ludwig Institute Clinical Trial Center, Division of Medical Oncology, Department of Medicine, Columbia University College of Physicians and Surgeons, New York, NY 10032, USA.
Brehm
Michelle
M
Metthez
Geneviève
G
Talbot
Susan
S
Dutoit
Valerie
V
Taub
Robert N
RN
Keohan
Mary-Louise
ML
Gure
Ali O
AO
Chen
Yao-Tseng
YT
Williamson
Barbara
B
Jungbluth
Achim A
AA
Old
Lloyd J
LJ
Hesdorffer
Charles S
CS
Valmori
Danila
D
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
D000951:Antigens, Neoplasm; D019496:Cancer Vaccines; D009363:Neoplasm Proteins; D012097:Repressor Proteins; D014614:Vaccines, Synthetic; C093962:synovial sarcoma X breakpoint proteins