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Published on: September 15, 2023
Cancer testis antigen Sperm Protein 17 as a new target for triple negative breast cancer immunotherapy
Leonardo Mirandola1, Elisa Pedretti1, Jose A Figueroa1
1Kiromic Inc., Houston, TX, USA.
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.
Insights
Sperm Protein 17 (SP17) is expressed in triple-negative breast cancer (TNBC) and can be targeted by the immune system. SP17-specific T cells efficiently kill breast cancer cells, offering a potential new immunotherapy for TNBC.
Area of Science:
- Oncology
- Immunology
- Molecular Biology
Background:
- Breast carcinoma poses a significant health challenge, with current treatments often ineffective for metastatic disease and triple-negative breast cancer (TNBC).
- Novel, less toxic therapies are urgently needed, particularly for TNBC, which is unresponsive to hormonal and antibody treatments.
- Cancer-testis antigens (CTA) are highly immunogenic and cancer-specific, making them promising targets for cancer immunotherapy.
Purpose of the Study:
- To evaluate Sperm Protein 17 (SP17) expression in breast cancer, including TNBC.
- To determine if SP17 can elicit an immune response and generate SP17-specific cytotoxic T lymphocytes (CTL) for potential immunotherapy.
Main Methods:
- SP17 expression was analyzed in breast cancer cell lines, primary invasive ductal carcinomas (including TNBC), and adjacent non-neoplastic breast tissue.
- The generation of SP17-specific CTLs was assessed *in vitro*.
- Anti-SP17 antibodies in patient sera were detected.
Main Results:
- SP17 is expressed in breast cancer cell lines and primary tumors, notably in the TNBC subtype.
- SP17 expression was absent in adjacent non-tumoral breast tissue but present in male germinal cells.
- Specific anti-SP17 antibodies were detected in patients' sera, and SP17-specific CTLs were generated *in vitro*.
- These SP17-specific CTLs demonstrated efficient killing of breast cancer cells.
Conclusions:
- SP17 is a promising tumor-associated antigen (TAA) for breast cancer immunotherapy, especially for TNBC.
- The presence of anti-SP17 antibodies and the generation of SP17-specific CTLs support SP17 as a viable target for immunotherapeutic strategies.
- Targeting SP17 could lead to novel, less toxic treatments for breast cancer, including the challenging TNBC subtype.
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