A Dual-Function DNA Vaccine Encoding Carcinoembryonic Antigen and CD40 Ligand Trimer Induces T Cell-Mediated Protective Immunity Against Colon Cancer in Carcinoembryonic Antigen-Transgenic Mice

摘要: A carcinoembryonic Ag (CEA)-based DNA vaccine encoding both CEA and CD40 ligand trimer achieved effective tumor-protective immunity against murine colon carcinoma in CEA-transgenic mice by activating naive T cells dendritic cells. Peripheral cell tolerance to was broken a prophylactic model this novel, dual-function vaccine, whose efficacy further enhanced boosts with recombinant Ab-IL-2 fusion protein (huKS1/4-IL-2). These conclusions are supported four lines of evidence. First, lethal challenge MC38-CEA-KS for the first time completely rejected 100% experimental animals treated oral gavage carried attenuated Salmonella typhimurium , followed five huKS1/4-IL-2. Second, specific activation indicated their marked up-regulation expression costimulatory molecules B7.1 (CD80), B7.2 (CD86), ICAM-1. Third, decisive increase over control values observed MHC class I Ag-restricted cytotoxicity CTLs from successfully vaccinated secretion proinflammatory cytokines IFN-γ IL-12. Fourth, augmented, as activity markers LFA-1, CD25, CD28, CD69. Taken together, these results suggest that combined tumor-targeted IL-2 may be promising strategy rational development DNA-based cancer vaccines future clinical applications.