Mesothelin-specific cell-based vaccine generates antigen-specific immunity and potent antitumor effects by combining with IL-12 immunomodulator.
Ovarian cancer is a gynecologic malignancy with a high mortality rate. In the present study, we developed a novel cell-based vaccine, Meso-VAX, to generate mesothelin antigen-specific immune responses and immunotherapy against ovarian cancer. Mesothelin, a secreted protein anchored at the cell membrane, has recently been identified as a potential new tumor antigen for ovarian cancer. In this study, mice vaccinated with Meso-VAX and adeno-associated virus (AAV)-IL-12 exhibited dramatic increases in the number of mesothelin-specific CD4(+) helper and CD8(+) cytotoxic T-cell precursors, higher titers of anti-mesothelin Abs and in vitro tumor killing activity, and all of these mice were tumor-free after 60 days of tumor challenge. In addition, a significant reduction in peritoneal tumors and longer survival were noted in the mice vaccinated with Meso-VAX combined with AAV-IL-12. CD4(+) helper and CD8(+) cytotoxic T lymphocytes were essential for the antitumor effect generated by Meso-VAX combined with AAV-IL-12. The post-vaccination sera of the mice vaccinated with Meso-VAX and AAV-IL-12 also showed mesothelin-specific complement-dependent cell-mediated cytotoxicity. Our results suggest that a Meso-VAX cell-based vaccine combined with AAV-IL-12 can generate antigen-specific immunological responses and antitumor effects on ovarian cancer.
Department of Obstetrics and Gynecology, Medicine College of Medicine, National Taiwan University, Taipei, Taiwan.|Department of Anesthesiology, Medicine College of Medicine, National Taiwan University, Taipei, Taiwan.
M-C
MC
Chang
Department of Obstetrics and Gynecology, Cathay General Hospital, Taipei, Taiwan.
Y-L
YL
Chen
Department of Obstetrics and Gynecology, Medicine College of Medicine, National Taiwan University, Taipei, Taiwan.
Y-C
YC
Chiang
Department of Obstetrics and Gynecology, Medicine College of Medicine, National Taiwan University, Taipei, Taiwan.
T-C
TC
Chen
Department of Obstetrics and Gynecology, Medicine College of Medicine, National Taiwan University, Taipei, Taiwan.
Y-C
YC
Tang
Department of Obstetrics and Gynecology, Medicine College of Medicine, National Taiwan University, Taipei, Taiwan.
C-A
CA
Chen
Department of Anesthesiology, Medicine College of Medicine, National Taiwan University, Taipei, Taiwan.
W-Z
WZ
Sun
Department of Obstetrics and Gynecology, Medicine College of Medicine, National Taiwan University, Taipei, Taiwan.|Graduate Institute of Clinical Medicine, Medicine College of Medicine, National Taiwan University, Taipei, Taiwan.|Graduate Institute of Oncology, Medicine College of Medicine, National Taiwan University, Taipei, Taiwan.
W-F
WF
Cheng
D000818:Animals; D000912:Antibodies, Neoplasm / Q000097:blood; D000951:Antigens, Neoplasm / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D019496:Cancer Vaccines / Q000276:immunology*; D045744:Cell Line, Tumor; D003602:Cytotoxicity, Immunologic; D000229:Dependovirus / Q000235:genetics; D005260:Female; D058851:GPI-Linked Proteins / Q000276:immunology*; D006801:Humans; D007167:Immunotherapy; D018664:Interleukin-12 / Q000276:immunology / Q000494:pharmacology*; D007376:Interleukin-2 / Q000276:immunology; D000090204:Mesothelin; D051379:Mice; D008810:Mice, Inbred C57BL; D010051:Ovarian Neoplasms / Q000188:drug therapy*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014611:Vaccination
D000912:Antibodies, Neoplasm; D000951:Antigens, Neoplasm; D019496:Cancer Vaccines; D058851:GPI-Linked Proteins; D007376:Interleukin-2; C000715528:Msln protein, mouse; D018664:Interleukin-12; D000090204:Mesothelin