Cancer testis antigen Sperm Protein 17 as a new target for triple negative breast cancer immunotherapy

// Leonardo Mirandola 1 , Elisa Pedretti 1 , Jose A. Figueroa 1 , Raffaella Chiaramonte 2 , Michela Colombo 2 , Caroline Chapman 3 , Fabio Grizzi 4 , Federica Patrinicola 4 , W. Martin Kast 5 , Diane D. Nguyen 1 , Rakhshanda Layeequr Rahman 6 , Naval Daver 7 , Peter Ruvolo 7 , Sean M. Post 7 , Robert S. Bresalier 8 and Maurizio Chiriva-Internati 1, 9 1 Kiromic Inc., Houston, TX, USA 2 Department of Health Sciences, Universita’ degli Studi di Milano, Milano, Italy 3 Bowel Cancer Screening Programme, Eastern Hub Queens Medical Centre, Nottingham University Hospitals, Nottingham, UK 4 Department of Immunology & Inflammation, Humanitas Clinical & Research Center, Milan, Italy 5 Departments of Obstetrics & Gynecology and Molecular Microbiology & Immunology, University of Southern California, Los Angeles, CA, USA 6 Texas Tech University Health Sciences Center, Amarillo Breast Center of Excellence, Amarillo, TX, USA 7 Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX, USA 8 Department of Gastroenterology, Hepatology and Nutrition, Division of Internal Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA 9 Department of Lymphoma & Myeloma, The University of Texas MD Anderson Cancer Center, Houston, TX, USA Correspondence to: Maurizio Chiriva-Internati, email: mchiriva@kiromic.com Keywords: cancer therapy, CTL, biomarker, CTA, breast cancer Received: June 30, 2016      Accepted: May 31, 2017      Published: August 10, 2017 ABSTRACT Breast carcinoma is a major health issue for millions of women. Current therapies have serious side effects, and are only partially effective in patients with metastatic tumors. Thus, the need for novel and less toxic therapies is urgent. Moreover, hormonal and antibody therapies effective in other subtypes are not effective in Triple Negative Breast Cancer (TNBC). Immunotherapeutic strategies directed against specific tumor-associated antigens (TAAs) and mediated by specific cytotoxic T lymphocytes (CTL) have been largely underexplored in this disease. Cancer-testis antigens (CTA) are a group of TAAs displaying the ideal characteristics of promising vaccine targets, i.e. strong immunogenicity and cancer specificity. The CTA, Sperm Protein 17 (SP17), has been found to be aberrantly expressed in different neoplasms, including ovarian and esophageal cancers, nervous system tumors and multiple myeloma, and has been suggested as a candidate target for immunotherapy. Here, we evaluated SP17 expression levels in breast cancer cell lines, invasive ductal breast carcinoma, including patients with TNBC, and adjacent non-neoplastic breast tissue, and determined whether SP17 was capable of generating SP17-specific cytotoxic T lymphocytes in vitro . We showed that SP17 is expressed in breast cancer cell lines and primary breast tumors and importantly in TNBC subtype, but not in adjacent non-tumoral breast tissue or unaffected tissues, except in male germinal cells. Furthermore, we detected specific anti-SP17 antibodies in patients’ sera and we generated SP17-specific, HLA class I-restricted, cytotoxic T lymphocytes capable of efficiently killing breast cancer cells.