Abstract
Lung cancer is the leading cause of cancer deaths in both genders worldwide, with an incidence only second to prostate cancer in men and breast cancer in women. The lethality of the disease highlights the urgent need for innovative therapeutic options. Immunotherapy can afford efficient and specific targeting of tumor cells, improving efficacy and reducing the side effects of current therapies. We have previously reported the aberrant expression of cancer/testis antigens (CTAs) in tumors of unrelated histological origin. In this study we investigated the expression and immunogenicity of the CTAs, Sperm Protein 17 (SP17), A-kinase anchor protein 4 (AKAP4) and Pituitary Tumor Transforming Gene 1 (PTTG1) in human non-small cell lung cancer (NSCLC) cell lines and primary tumors. We found that SP17, AKAP4 and PTTG1 are aberrantly expressed in cancer samples, compared to normal lung cell lines and tissues. We established the immunogenicity of these CTAs by measuring CTA-specific autoantibodies in patients' sera and generating CTA-specific autologous cytotoxic lymphocytes from patients' peripheral blood mononuclear cells. Our results provide proof of principle that the CTAs SP17/AKAP4/PTTG1 are expressed in both human NSCLC cell lines and primary tumors and can elicit an immunogenic response in lung cancer patients.
Highlights
Lung cancer is the leading cause of cancer-related deaths worldwide, with approximately 226,160 new cases and 160,340 deaths in the Unites States in 2013[1]
Our results provide proof of principle that the cancer/testis antigens (CTAs) Sperm Protein 17 (SP17)/A-kinase anchor protein 4 (AKAP4)/Pituitary Tumor Transforming Gene 1 (PTTG1) are expressed in both human non-small cell lung cancer (NSCLC) cell lines and primary tumors and can elicit an immunogenic response in lung cancer patients
We have previously demonstrated that the CTAs SP17, AKAP4, Ropporin, and PTTG1 are potential immunotherapeutic targets in ovarian cancer, multiple myeloma, and prostate cancer [3, 10,11,12]
Summary
Lung cancer is the leading cause of cancer-related deaths worldwide, with approximately 226,160 new cases and 160,340 deaths in the Unites States in 2013[1]. Cancer/testis antigens (CTAs) are a family of proteins with testis-restricted expression and negligible expression www.impactjournals.com/oncotarget in normal tissues. The CTAs NY-ESO-1 and MAGE-A2/3/4/6 have been detected in NSCLC primary tumors and their immunogenicity suggests they are promising targets for the development of potentially effective lung cancer vaccines [7,8,9]. In this study we evaluated RNA and protein expression patterns of SP17, AKAP4 and PTTG1 in NSCLC cell lines and primary tumor samples from NSCLC patients, compared to normal lung cells and tissues. We determined the immunogenicity of these CTAs by measuring CTA-specific antibodies (Abs) in the sera of lung cancer patients and generating CTA-specific cytotoxic anti-tumor responses in vitro, using autologous peripheral blood mononuclear cells (PBMCs)
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