Cancer testis antigen vaccination affords long-term protection in a murine model of ovarian cancer.
Sperm protein (Sp17) is an attractive target for ovarian cancer (OC) vaccines because of its over-expression in primary as well as in metastatic lesions, at all stages of the disease. Our studies suggest that a Sp17-based vaccine can induce an enduring defense against OC development in C57BL/6 mice with ID8 cells, following prophylactic and therapeutic treatments. This is the first time that a mouse counterpart of a cancer testis antigen (Sp17) was shown to be expressed in an OC mouse model, and that vaccination against this antigen significantly controlled tumor growth. Our study shows that the CpG-adjuvated Sp17 vaccine overcomes the issue of immunologic tolerance, the major barrier to the development of effective immunotherapy for OC. Furthermore, this study provides a better understanding of OC biology by showing that Th-17 cells activation and contemporary immunosuppressive T-reg cells inhibition is required for vaccine efficacy. Taken together, these results indicate that prophylactic and therapeutic vaccinations can induce long-standing protection against OC and delay tumor growth, suggesting that this strategy may provide additional treatments of human OC and the prevention of disease onset in women with a family history of OC.
Chiriva-Internati
Maurizio
M
Division of Hematology and Oncology, Texas Tech University Health Sciences Center, Lubbock, Texas, United States of America. maurizio.chiriva@ttuhsc.edu
Yu
Yuefei
Y
Mirandola
Leonardo
L
Jenkins
Marjorie R
MR
Chapman
Caroline
C
Cannon
Martin
M
Cobos
Everardo
E
Kast
W Martin
WM
D000818:Animals; D000951:Antigens, Neoplasm / Q000276:immunology*; D019496:Cancer Vaccines / Q000276:immunology*; D002460:Cell Line; D003602:Cytotoxicity, Immunologic / Q000276:immunology; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D007274:Injections, Intraperitoneal; D007371:Interferon-gamma / Q000097:blood; D008285:Major Histocompatibility Complex / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D010051:Ovarian Neoplasms / Q000097:blood / Q000276:immunology* / Q000473:pathology / Q000517:prevention & control*; D016019:Survival Analysis; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000097:blood; D014611:Vaccination
D000951:Antigens, Neoplasm; D019496:Cancer Vaccines; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma