Novel antigens in non-small cell lung cancer: SP17, AKAP4, and PTTG1 are potential immunotherapeutic targets
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Leonardo Mirandola1,2, Jose A. Figueroa1,3, Tam T. Phan1, Fabio Grizzi4, Minji Kim1, Rakhshanda Layeequr Rahman5, Marjorie R. Jenkins1,2, Everardo Cobos1,2,3, Cynthia Jumper6, Raed Alalawi6 and Maurizio Chiriva-Internati1,2,3
1 Division of Hematology & Oncology and Southwest Cancer Treatment and Research Center, Texas Tech University, Lubbock, TX, USA
2 Laura W. Bush Institute for Women’s Health and Center for Women’s Health and Gender-Based Medicine, Amarillo, TX, USA
3 Kiromic, LLC. Lubbock, TX, USA
4 Humanitas Clinical and Research Center, Milano, Italy
5 Division of Surgical Oncology, Texas Tech University Medical Center, Amarillo, TX, USA
6 Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Texas Tech University Health Sciences Center, Lubbock, TX, USA
Maurizio Chiriva-Internati, email:
Keywords: cancer/testis antigens, lung cancer, cancer vaccines
Received: September 29, 2014 Accepted: November 15, 2014 Published: February 20, 2015
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.
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