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

Leonardo Mirandola, Elisa Pedretti, Jose A Figueroa, Raffaella Chiaramonte, Michela Colombo, Caroline Chapman, Fabio Grizzi, Federica Patrinicola, W Martin Kast, Diane D Nguyen, Rakhshanda Layeequr Rahman, Naval Daver, Peter Ruvolo, Sean M Post, Robert S Bresalier, Maurizio Chiriva-Internati

Research output: Contribution to journalArticle

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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 lymphocytesin 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.

Original languageEnglish
Pages (from-to)74378-74390
Number of pages13
JournalOncotarget
Volume8
Issue number43
DOIs
Publication statusPublished - Sep 26 2017

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Triple Negative Breast Neoplasms
Testicular Neoplasms
Immunotherapy
Spermatozoa
Antigens
Breast Neoplasms
Proteins
Cytotoxic T-Lymphocytes
Neoplasm Antigens
Breast
Nervous System Neoplasms
Carcinoma, Ductal, Breast
Cell Line
Neoplasms
Antibodies
Poisons
Esophageal Neoplasms
Multiple Myeloma
Ovarian Neoplasms
Therapeutics

Keywords

  • Journal Article

Cite this

Mirandola, L., Pedretti, E., Figueroa, J. A., Chiaramonte, R., Colombo, M., Chapman, C., ... Chiriva-Internati, M. (2017). Cancer testis antigen Sperm Protein 17 as a new target for triple negative breast cancer immunotherapy. Oncotarget, 8(43), 74378-74390. https://doi.org/10.18632/oncotarget.20102

Cancer testis antigen Sperm Protein 17 as a new target for triple negative breast cancer immunotherapy. / Mirandola, Leonardo; Pedretti, Elisa; Figueroa, Jose A; Chiaramonte, Raffaella; Colombo, Michela; Chapman, Caroline; Grizzi, Fabio; Patrinicola, Federica; Kast, W Martin; Nguyen, Diane D; Rahman, Rakhshanda Layeequr; Daver, Naval; Ruvolo, Peter; Post, Sean M; Bresalier, Robert S; Chiriva-Internati, Maurizio.

In: Oncotarget, Vol. 8, No. 43, 26.09.2017, p. 74378-74390.

Research output: Contribution to journalArticle

Mirandola, L, Pedretti, E, Figueroa, JA, Chiaramonte, R, Colombo, M, Chapman, C, Grizzi, F, Patrinicola, F, Kast, WM, Nguyen, DD, Rahman, RL, Daver, N, Ruvolo, P, Post, SM, Bresalier, RS & Chiriva-Internati, M 2017, 'Cancer testis antigen Sperm Protein 17 as a new target for triple negative breast cancer immunotherapy', Oncotarget, vol. 8, no. 43, pp. 74378-74390. https://doi.org/10.18632/oncotarget.20102
Mirandola L, Pedretti E, Figueroa JA, Chiaramonte R, Colombo M, Chapman C et al. Cancer testis antigen Sperm Protein 17 as a new target for triple negative breast cancer immunotherapy. Oncotarget. 2017 Sep 26;8(43):74378-74390. https://doi.org/10.18632/oncotarget.20102
Mirandola, Leonardo ; Pedretti, Elisa ; Figueroa, Jose A ; Chiaramonte, Raffaella ; Colombo, Michela ; Chapman, Caroline ; Grizzi, Fabio ; Patrinicola, Federica ; Kast, W Martin ; Nguyen, Diane D ; Rahman, Rakhshanda Layeequr ; Daver, Naval ; Ruvolo, Peter ; Post, Sean M ; Bresalier, Robert S ; Chiriva-Internati, Maurizio. / Cancer testis antigen Sperm Protein 17 as a new target for triple negative breast cancer immunotherapy. In: Oncotarget. 2017 ; Vol. 8, No. 43. pp. 74378-74390.
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AU - Nguyen, Diane D

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AU - Daver, Naval

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