RT Journal Article
SR Electronic
T1 Sperm-Derived SPANX-B Is a Clinically Relevant Tumor Antigen That Is Expressed in Human Tumors and Readily Recognized by Human CD4<sup>+</sup> and CD8<sup>+</sup> T Cells
JF Clinical Cancer Research
JO Clin Cancer Res
FD American Association for Cancer Research
SP 1954
OP 1963
DO 10.1158/1078-0432.CCR-08-1290
VO 15
IS 6
A1 Almanzar, Giovanni
A1 Olkhanud, Purevdorj B.
A1 Bodogai, Monica
A1 Dell'Agnola, Chiara
A1 Baatar, Dolgor
A1 Hewitt, Stephen M.
A1 Ghimenton, Claudio
A1 Tummala, Mohan K.
A1 Weeraratna, Ashani T.
A1 Hoek, Keith Sean
A1 Kouprina, Natalay
A1 Larionov, Vladimir
A1 Biragyn, Arya
YR 2009
UL http://clincancerres.aacrjournals.org/content/15/6/1954.abstract
AB Purpose: 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. Experimental Design: 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-B12-23) and two HLA-A2-restricted Pep-2 and Pep-4 epitopes (SPANX-B23-31 and SPANX-B57-65, 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.