title: Sperm-derived SPANX-B is a clinically relevant tumor antigen that is expressed in human tumors and readily recognized by human CD4+ and CD8+ T cells.
abstract: OBJECTIVE
  The sperm-derived SPANX family proteins can be found expressed in human tumors. Here, we aimed to perform a comprehensive study to evaluate immunotherapeutic relevance of one of its members, SPANX-B. We wanted to test its expression pattern in human tumors and to evaluate CD4(+) and CD8(+) T-cell responses in healthy humans after in vitro immunizations.
  
  
  METHODS
  Expression of SPANX-B in human malignancies, including a multitumor tissue array of 145 primary tumors, was assessed using reverse transcription-PCR, Western blotting, and immunohistochemical analysis. T-cell immunogenicity and immunodominant epitopes of SPANX-B were studied using in vitro immunizations of healthy human donor-derived leukocytes.
  
  
  RESULTS
  SPANX-B was abundantly expressed in melanoma and carcinomas of lung, ovary, colon, and breast. In melanoma, tissue array data indicated that it was expressed in advanced and metastatic disease. Unlike most tumor-associated antigens, SPANX-B was an immunogenic antigen that was recognized by circulating T-cell precursors in healthy humans. Importantly, these T cells were readily expanded to generate SPANX-B-specific helper CD4(+) and cytolytic CD8(+) T cells that recognized unique immunodominant epitopes: at least one HLA-DR-restricted Pep-9 epitope (SPANX-B(12-23)) and two HLA-A2-restricted Pep-2 and Pep-4 epitopes (SPANX-B(23-31) and SPANX-B(57-65), respectively). CD8(+) T cells were fully functional to recognize and lyse HLA-A2-expressing tumors, including primary human melanomas.
  
  
  CONCLUSIONS
  SPANX-B is an immunogenic sperm-derived antigen that is expressed in several human tumors. SPANX-B is also efficiently recognized by the human T-cell immune arm, indicating its significant value for the development of protective and therapeutic cancer vaccines.
authors.affiliation: Laboratory of Immunology and Clinical Research Branch, National Institute on Aging, Baltimore, Maryland, USA.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Almanzar
authors.forename: Purevdorj B
authors.initials: PB
authors.lastname: Olkhanud
authors.forename: Monica
authors.initials: M
authors.lastname: Bodogai
authors.forename: Chiara
authors.initials: C
authors.lastname: Dell'agnola
authors.forename: Dolgor
authors.initials: D
authors.lastname: Baatar
authors.forename: Stephen M
authors.initials: SM
authors.lastname: Hewitt
authors.forename: Claudio
authors.initials: C
authors.lastname: Ghimenton
authors.forename: Mohan K
authors.initials: MK
authors.lastname: Tummala
authors.forename: Ashani T
authors.initials: AT
authors.lastname: Weeraratna
authors.forename: Keith Sean
authors.initials: KS
authors.lastname: Hoek
authors.forename: Natalay
authors.initials: N
authors.lastname: Kouprina
authors.forename: Vladimir
authors.initials: V
authors.lastname: Larionov
authors.forename: Arya
authors.initials: A
authors.lastname: Biragyn
mesh_terms: D000595:Amino Acid Sequence; D000951:Antigens, Neoplasm / Q000032:analysis*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D019496:Cancer Vaccines / Q000276:immunology; D006801:Humans; D016056:Immunodominant Epitopes; D008969:Molecular Sequence Data; D009369:Neoplasms / Q000276:immunology* / Q000628:therapy; D009687:Nuclear Proteins / Q000032:analysis* / Q000276:immunology
chemical_list: D000951:Antigens, Neoplasm; D019496:Cancer Vaccines; D016056:Immunodominant Epitopes; D009687:Nuclear Proteins; C518957:SPANXB1 protein, human