A loss of antitumor therapeutic activity of CEA DNA vaccines is associated with the lack of tumor cells' antigen presentation to Ag-specific CTLs in a colon cancer model. Issue 2 (28th January 2015)

• Record Type: Journal Article
• Authors: Ahn, Euri; Kim, Ha; Han, Kyusun Torque; Sin, Jeong-Im
• Is Part Of: Cancer letters. Volume 356:Issue 2(2015)Part B
• Page Start: 676
• Page End: 685
• Publication Date: 2015-01-28
• Subjects: CEA carcinoembryonic antigen -- CFSE carboxyfluorescein diacetate succinimidyl ester -- EP electroporation -- HPV human papillomavirus -- IM intramuscular -- IT intratumoral -- i.t intratumorally -- LDH lactate dehydrogenase -- PBS phosphate-buffered saline -- s.c subcutaneously; Antitumor immunity -- CEA -- Colon cancer -- DNA vaccines -- Tumor immune evasion; Cancer -- Periodicals; Neoplasms -- Periodicals; Cancer -- Périodiques; Electronic journals; 616.994
• DOI: 10.1016/j.canlet.2014.10.019
• Languages: English
• ISSNs: 0304-3835

Abstract

Abstract: Human colon cancers express carcinoembryonic antigen (CEA). Thus, CEA has been considered as a potential vaccine target for immune therapy against colon cancer. In this study, CEA DNA vaccines plus anti-4-1BB Abs treatment was found to increase Ag-specific CTL activity and antitumor protective responses to MC32 cells. However, CEA DNA vaccines alone displayed few antitumor therapeutic effects while significantly inducing Ag-specific CTL responses. Anti-4-1BB Abs alone displayed antitumor therapeutic effects. Intratumoral electroporation with IL-12 cDNA also showed antitumor therapeutic activity against MC32 cells in a CD8+ T cell-dependent and CEA-non-specific manner, suggesting that established MC32 cells are still susceptible to CTL-mediated killing. Finally, our in vitro assays (Western blot assay, IFN-γ, CTL and apoptosis assays, FACS analysis) and animal studies demonstrated that a lack of antitumor therapeutic activity of CEA DNA vaccines might result from acquisition of tumor cell resistance to Ag-specific CTL-mediated killing through the loss of tumor cells' antigen presentation to Ag-specific CTLs. Taken together, these data show that MC32 cells may resist CEA DNA vaccination by their loss of antigen presentation to CEA-specific CTLs in the therapeutic model.