Maximizing CD8+ T cell responses elicited by peptide vaccines containing CpG oligodeoxynucleotides.
We assessed the ability of several factors to increase the size of tumor-antigen-specific CD8(+) T cell responses elicited by vaccines incorporating peptides and CpG-containing oligodeoxynucleotides (CpG). Neither granulocyte-macrophage colony-stimulating factor (GM-CSF) nor an immunogenic MHC class II-presented "helper" peptide increased the size of epitope-specific CD8+ T cell responses elicited by peptide+CpG-containing vaccines. In contrast, low-dose subcutaneous interleukin (IL)-2 dramatically increased the size of splenic and peripheral blood epitope-specific CD8(+) T cell responses generated by peptide+CpG-containing vaccines. Moreover, peptide+CpG-containing vaccines plus low-dose IL-2 mediated anti-tumor immunity. A prime-boost vaccination schedule elicited larger CD8(+) T cell responses than a weekly vaccination schedule. Including larger doses of peptide in vaccines led to larger vaccine-elicited CD8(+) T cell responses. Clinical trials of CpG-containing peptide vaccines are ongoing. These findings suggest strategies to increase the size of CD8(+) T cell responses generated by CpG-containing peptide vaccines that could be tested in future clinical trials.
Kochenderfer
James N
JN
Experimental Transplantation and Immunology Branch, National Cancer Institute, National Institutes of Health 10 Center Drive CRC 3-3288 Bethesda, MD 20892, USA. kochendj@mail.nih.gov
Chien
Christopher D
CD
Simpson
Jessica L
JL
Gress
Ronald E
RE
D000276:Adjuvants, Immunologic / Q000494:pharmacology; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D019496:Cancer Vaccines / Q000276:immunology; D045744:Cell Line, Tumor; D004306:Dose-Response Relationship, Immunologic; D000939:Epitopes; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000276:immunology / Q000494:pharmacology; D007115:Immunization Schedule; D007376:Interleukin-2 / Q000276:immunology / Q000494:pharmacology; D019746:Intramolecular Oxidoreductases / Q000276:immunology / Q000494:pharmacology; D008546:Melanoma, Experimental / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D009838:Oligodeoxyribonucleotides / Q000276:immunology*; D010446:Peptide Fragments / Q000276:immunology / Q000494:pharmacology; D022223:Vaccines, Subunit / Q000276:immunology*
D000276:Adjuvants, Immunologic; C408982:CPG-oligonucleotide; D019496:Cancer Vaccines; D000939:Epitopes; D007376:Interleukin-2; D009838:Oligodeoxyribonucleotides; D010446:Peptide Fragments; D022223:Vaccines, Subunit; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D019746:Intramolecular Oxidoreductases; C042501:dopachrome isomerase