CD8 + T‐Cell Tolerance can be Broken by an Adenoviral Vaccine While CD4 + T‐Cell Tolerance is Broken by Additional Co‐administration of a Toll‐Like Receptor Ligand

T‐cell tolerance to tumor antigens is a considerable challenge to cancer immunotherapy. The existence of a murine model transgenic for human carcinoembryonic antigen (CEA) allows CEA vaccination efficacy to be studied in a physiologically tolerant context. Immunization of CEA‐transgenic mice with an adenoviral vector coding for CEA induced a significant CD8 + T‐cell response specific to CEA but failed to induce CEA‐specific CD4 + T cells and antibodies. To overcome CD4 + T‐cell tolerance, we explored the effect of adjuvants inducing in vivo dendritic cell maturation. Two different Toll‐like receptor ligands, monophosphoryl lipid A (MPL) and CpG motif‐containing oligodeoxynucleotides (CpG‐ODN), were tested. CD4 + ‐mediated IFN‐γ production was induced in the CEA‐transgenic mice only when the genetic immunization was performed in the presence of these adjuvants. Moreover, CpG‐ODN had a greater effect than MPL in inducing CD4 + T‐cell response and enabling anti‐CEA antibody production.