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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
Author(s) -
Salucci V.,
Mennuni C.,
Calvaruso F.,
Cerino R.,
Neuner P.,
Ciliberto G.,
La Monica N.,
Scarselli E.
Publication year - 2006
Publication title -
scandinavian journal of immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.934
H-Index - 88
eISSN - 1365-3083
pISSN - 0300-9475
DOI - 10.1111/j.1365-3083.2006.01706.x
Subject(s) - antigen , t cell , cd8 , immunotherapy , biology , immune tolerance , cytotoxic t cell , immunology , microbiology and biotechnology , cancer research , immune system , in vitro , biochemistry
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.