CpG are efficient adjuvants for specific CTL induction against tumor antigen-derived peptide.
The identification of CTL-defined tumor-associated Ags has allowed the development of new strategies for cancer immunotherapy. To potentiate the CTL responses, peptide-based vaccines require the coadministration of adjuvants. Because oligodeoxynucleotides (ODN) containing CpG motifs are strong immunostimulators, we analyzed the ability of CpG ODN to act as adjuvant of the CTL response against tumor-derived synthetic peptide in the absence or presence of IFA. Mice transgenic for a chimeric MHC class I molecule were immunized with a peptide analog of MART-1/Melan-A(26-35) in the presence of CpG ODN alone or CpG ODN emulsified in IFA. The CTL response was monitored ex vivo by tetramer staining of lymphocytes. In blood, spleen, and lymph nodes, peptide mixed with CpG ODN alone was able to elicit a stronger systemic CTL response as compared with peptide emulsified in IFA. Moreover, CpG ODN in combination with IFA further enhanced the CTL response in terms of the frequency of tetramer+CD8+ T cells ex vivo. The CTL induced in vivo against peptide analog in the presence of CpG ODN are functional, as they were able to recognize and kill melanoma cells in vitro. Overall, these results indicate that CpG ODN by itself is a good candidate adjuvant of CTL response and can also enhance the effect of classical adjuvant.
Miconnet
Isabelle
I
Ludwig Institute for Cancer Research, University of Lausanne, Hôpital Orthopédique Niveau 5 Est, Avenue Pierre Decker 4, Epalinges, 1005 Lausanne, Switzerland.
Koenig
Sylvain
S
Speiser
Daniel
D
Krieg
Arthur
A
Guillaume
Philippe
P
Cerottini
Jean-Charles
JC
Romero
Pedro
P
D000276:Adjuvants, Immunologic / Q000008:administration & dosage*; D000818:Animals; D000951:Antigens, Neoplasm / Q000494:pharmacology*; D019496:Cancer Vaccines / Q000008:administration & dosage / Q000276:immunology; D003601:Cytotoxicity Tests, Immunologic / Q000706:statistics & numerical data; D018984:Epitopes, T-Lymphocyte / Q000032:analysis / Q000276:immunology*; D015789:HLA-A2 Antigen / Q000032:analysis; D006801:Humans; D007279:Injections, Subcutaneous; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009363:Neoplasm Proteins / Q000008:administration & dosage / Q000276:immunology*; D009838:Oligodeoxyribonucleotides / Q000008:administration & dosage / Q000276:immunology*; D010446:Peptide Fragments / Q000008:administration & dosage / Q000276:immunology*; D013194:Staining and Labeling / Q000379:methods / Q000706:statistics & numerical data; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014407:Tumor Cells, Cultured
D000276:Adjuvants, Immunologic; D000951:Antigens, Neoplasm; C408982:CPG-oligonucleotide; D019496:Cancer Vaccines; D018984:Epitopes, T-Lymphocyte; D015789:HLA-A2 Antigen; D009363:Neoplasm Proteins; D009838:Oligodeoxyribonucleotides; D010446:Peptide Fragments