The present study uses an in vivo murine tumor model expressing the human HER -2 / neu antigen to evaluate the potential vaccine using dendritic cells ( DCs ) infected with adenovirus AdVHER -2. We first investigated whether infected DCs ( DC HER -2 ) engineered to express HER -2 / neu could induce HER -2 / neu -specific immune responses. Our data showed that ( i ) AdVHER2 -infected DC HER -2 expressed HER -2 / neu by Western blot and flow cytometric analysis, and ( ii ) vaccination of mice with DC HER -2 induced HER -2 / neu -specific cytotoxic T -lymphocyte ( CTL ) responses, but protected only 25% of vaccinated mice from challenge of 3Â10 5 MCA26 / HER -2 tumor cells. Further, to enhance the efficacy of DC HER -2 vaccine, we coinfected DCs with both AdVHER -2 and AdVTNF -a. The infected DCs ( DC HER -2 / TNF -a ) displayed the expression of both HER -2 / neu and TNF -a by flow cytometric and ELISA analysis. We next investigated whether DC HER -2 / TNF -a could induce stronger HER -2 / neu -specific immune responses. We found that DC HER -2 / TNF -a displayed up -regulation of immunologically important CD40, CD86, and ICAM -I molecules compared with DC HER -2 , indicating that the former ones are more mature forms of DCs. Vaccination of DC HER -2 / TNF -a induced stronger allogeneic T -cell proliferation and 36% enhanced HER -2 / neu -specific T -cell responses in vitro than DC HER -2 cells. More importantly, it stimulated the significant anti -HER -2 / neu immunity in vivo, which protected 8 / 8 mice from challenge of 3Â10 5 MCA26 / HER -2 tumor cells. Therefore, DCs genetically engineered to express both the tumor antigen and cytokines such as TNF -a as an immunoadjuvant are likely to represent a new direction in DC vaccine of cancer.

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Clinical Pharmacology & Therapeutics (1996) 59, 184–184; doi:

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