Novel antigens in non-small cell lung cancer: SP17, AKAP4, and PTTG1 are potential immunotherapeutic targets.
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.
Division of Hematology & Oncology and Southwest Cancer Treatment and Research Center, Texas Tech University, Lubbock, TX, USA.|Laura W. Bush Institute for Women's Health and Center for Women's Health and Gender-Based Medicine, Amarillo, TX, USA.
Leonardo
L
Mirandola
Division of Hematology & Oncology and Southwest Cancer Treatment and Research Center, Texas Tech University, Lubbock, TX, USA.|Kiromic, LLC. Lubbock, TX, USA.
Jose A
JA
Figueroa
Division of Hematology & Oncology and Southwest Cancer Treatment and Research Center, Texas Tech University, Lubbock, TX, USA.
Tam T
TT
Phan
Humanitas Clinical and Research Center, Milano, Italy.
Fabio
F
Grizzi
Division of Hematology & Oncology and Southwest Cancer Treatment and Research Center, Texas Tech University, Lubbock, TX, USA.
Minji
M
Kim
Division of Surgical Oncology, Texas Tech University Medical Center, Amarillo, TX, USA.
Rakhshanda Layeequr
RL
Rahman
Division of Hematology & Oncology and Southwest Cancer Treatment and Research Center, Texas Tech University, Lubbock, TX, USA.|Laura W. Bush Institute for Women's Health and Center for Women's Health and Gender-Based Medicine, Amarillo, TX, USA.
Marjorie R
MR
Jenkins
Division of Hematology & Oncology and Southwest Cancer Treatment and Research Center, Texas Tech University, Lubbock, TX, USA.|Laura W. Bush Institute for Women's Health and Center for Women's Health and Gender-Based Medicine, Amarillo, TX, USA.|Kiromic, LLC. Lubbock, TX, USA.
Everardo
E
Cobos
Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Texas Tech University Health Sciences Center, Lubbock, TX, USA.
Cynthia
C
Jumper
Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Texas Tech University Health Sciences Center, Lubbock, TX, USA.
Raed
R
Alalawi
Division of Hematology & Oncology and Southwest Cancer Treatment and Research Center, Texas Tech University, Lubbock, TX, USA.|Laura W. Bush Institute for Women's Health and Center for Women's Health and Gender-Based Medicine, Amarillo, TX, USA.|Kiromic, LLC. Lubbock, TX, USA.
Maurizio
M
Chiriva-Internati
D054758:A Kinase Anchor Proteins / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D000368:Aged; D000369:Aged, 80 and over; D000951:Antigens, Neoplasm / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D000954:Antigens, Surface / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D001323:Autoantibodies / Q000097:blood; D002148:Calmodulin-Binding Proteins; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics / Q000276:immunology* / Q000378:metabolism / Q000473:pathology / Q000628:therapy; D002352:Carrier Proteins / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D016022:Case-Control Studies; D045744:Cell Line, Tumor; D018920:Coculture Techniques; D003602:Cytotoxicity, Immunologic; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007167:Immunotherapy / Q000379:methods; D008175:Lung Neoplasms / Q000235:genetics / Q000276:immunology* / Q000378:metabolism / Q000473:pathology / Q000628:therapy; D008297:Male; D008565:Membrane Proteins; D008875:Middle Aged; D012333:RNA, Messenger / Q000378:metabolism; D064249:Securin / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology / Q000378:metabolism; D015854:Up-Regulation
D054758:A Kinase Anchor Proteins; C485480:AKAP4 protein, human; D000951:Antigens, Neoplasm; D000954:Antigens, Surface; D001323:Autoantibodies; D002148:Calmodulin-Binding Proteins; D002352:Carrier Proteins; D008565:Membrane Proteins; D012333:RNA, Messenger; C090172:SPA17 protein, human; D064249:Securin; C578002:pituitary tumor-transforming protein 1, human