Antigen-specific CD8+ T lymphocytes generated from a DNA vaccine control tumors through the Fas-FasL pathway
Journal
Molecular Therapy
Journal Volume
960
Journal Issue
968
Pages
960-968
Date Issued
2005
Author(s)
Abstract
Human papillomavirus, particularly type 16, and its oncogenic proteins, E6 and E7, are consistently expressed in most cervical cancers. One of the major issues facing cancer immunotherapy is that many human cancers evade the immune system by downregulating the expression of Fas molecules. An E7-expressing murine tumor model with a downregulated Fas expression - TC-1 P3(A15) tumors - was created. A DNA vaccine encoding calreticulin linked to E7 (CRT/E7) was able to generate protective and therapeutic antitumor effects against TC-1 P3(A15) tumors. In vitro Ab depletion and in vivo adoptive experiments showed that the antitumor effect of E7-specific CD8+ T lymphocytes against the TC-1 P3(A15) tumor cells was through the Fas-FasL-dependent CTL effector mechanism, and the TC-1 P3(A15) tumor cells needed higher numbers of antigen-specific CD8+ T lymphocytes for in vivo elimination. Our results demonstrated that chimeric CRT/E7 DNA vaccine resulted in control of tumors with downregulated Fas expression, highlighting the importance of the Fas-FasL pathway in the potent antitumor effect of antigen-specific CD8+ cytotoxic T lymphocytes and the role of Fas as part of in vivo tumor evasion. Copyright ? The American Society of Gene Therapy.
SDGs
Other Subjects
calreticulin; DNA vaccine; Fas antigen; FAS ligand; protein E7; animal cell; animal experiment; animal model; antigen expression; antineoplastic activity; article; cancer; cancer control; cancer immunotherapy; cancer inhibition; controlled study; down regulation; female; in vitro study; in vivo study; mouse; nonhuman; protection; T lymphocyte; upregulation; Animals; Antigens, CD95; Cancer Vaccines; CD8-Positive T-Lymphocytes; Cell Line, Tumor; Down-Regulation; Fas Ligand Protein; Female; Gene Therapy; Histocompatibility Antigens Class I; Interferon Type II; Membrane Glycoproteins; Mice; Mice, Inbred C57BL; Neoplasms, Experimental; T-Lymphocytes, Cytotoxic; Tumor Necrosis Factors; Vaccines, DNA; Animalia; Human papillomavirus; Murinae
Type
journal article