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.
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.
Almanzar
Giovanni
G
Laboratory of Immunology and Clinical Research Branch, National Institute on Aging, Baltimore, Maryland, USA.
Olkhanud
Purevdorj B
PB
Bodogai
Monica
M
Dell'agnola
Chiara
C
Baatar
Dolgor
D
Hewitt
Stephen M
SM
Ghimenton
Claudio
C
Tummala
Mohan K
MK
Weeraratna
Ashani T
AT
Hoek
Keith Sean
KS
Kouprina
Natalay
N
Larionov
Vladimir
V
Biragyn
Arya
A
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
D000951:Antigens, Neoplasm; D019496:Cancer Vaccines; D016056:Immunodominant Epitopes; D009687:Nuclear Proteins; C518957:SPANXB1 protein, human