Mesothelin-specific cell-based vaccine generates antigen-specific immunity and potent antitumor effects by combining with IL-12 immunomodulator
Journal
Gene Therapy
Journal Volume
23
Journal Issue
1
Pages
38-49
Date Issued
2016
Author(s)
Chang M.-C.
Chen T.-C.
Tang Y.-C.
Abstract
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. ? 2016 Macmillan Publishers Limited.
SDGs
Other Subjects
Adeno associated virus interleukin 12; cancer vaccine; meso vax; mesothelin antibody; protein antibody; tumor antigen; unclassified drug; cancer antibody; cancer vaccine; glycosylphosphatidylinositol anchored protein; interleukin 12; interleukin 2; mesothelin; tumor antigen; Adeno associated virus; animal cell; animal experiment; animal model; antibody titer; antineoplastic activity; Article; cancer immunotherapy; cancer survival; CD4 lymphocyte count; CD8+ T lymphocyte; cell membrane; drug potency; female; immune response; immunomodulation; in vitro study; mouse; nonhuman; ovary cancer; peritoneum tumor; pre T lymphocyte; priority journal; animal; blood; C57BL mouse; CD4+ T lymphocyte; cytotoxic T lymphocyte; cytotoxicity; Dependoparvovirus; genetics; human; immunology; immunotherapy; Ovarian Neoplasms; tumor cell line; vaccination; Animals; Antibodies, Neoplasm; Antigens, Neoplasm; Cancer Vaccines; CD4-Positive T-Lymphocytes; CD8-Positive T-Lymphocytes; Cell Line, Tumor; Cytotoxicity, Immunologic; Dependovirus; Female; GPI-Linked Proteins; Humans; Immunotherapy; Interleukin-12; Interleukin-2; Mice; Mice, Inbred C57BL; Ovarian Neoplasms; T-Lymphocytes, Cytotoxic; Vaccination
Type
journal article