| RRC ID |
31869
|
| 著者 |
Masuko K, Wakita D, Togashi Y, Kita T, Kitamura H, Nishimura T.
|
| タイトル |
Artificially synthesized helper/killer-hybrid epitope long peptide (H/K-HELP): preparation and immunological analysis of vaccine efficacy.
|
| ジャーナル |
Immunol Lett
|
| Abstract |
To elucidate the immunologic mechanisms of artificially synthesized helper/killer-hybrid epitope long peptide (H/K-HELP), which indicated a great vaccine efficacy in human cancers, we prepared ovalbumin (OVA)-H/K-HELP by conjugating killer and helper epitopes of OVA-model tumor antigen via a glycine-linker. Vaccination of C57BL/6 mice with OVA-H/K-HELP (30 amino acids) but not with short peptides mixture of class I-binding peptide (8 amino-acids) and class II-binding peptide (17 amino-acids) combined with adjuvant CpG-ODN (cytosine-phosphorothioate-guanine oligodeoxynucleotides), induced higher numbers of OVA-tetramer-positive CTL with concomitant activation of IFN-γ-producing CD4(+) Th1 cells. However, replacement of glycine-linker of OVA-H/K-HELP with other peptide-linker caused a significant decrease of vaccine efficacy of OVA-H/K-HELP. In combination with adjuvant CpG-ODN, OVA-H/KHELP exhibited greater vaccine efficacy compared with short peptides vaccine, in both preventive and therapeutic vaccine models against OVA-expressing EG-7 tumor. The elevated vaccine efficacy of OVAH/K-HELP might be derived from the following mechanisms: (i) selective presentation by only professional dendritic cells (DC) in vaccinated draining lymph node (dLN); (ii) a long-term sustained antigen presentation exerted by DC to stimulate both CTL and Th1 cells; (iii) formation of three cells interaction among DC, Th and CTL. In comparative study, H/K-HELP indicated stronger therapeutic vaccine efficacy compared with that of extended class I synthetic long peptide, indicating that both the length of peptide and the presence of Th epitope peptide were crucial aspects for preparing artificially synthesized H/K-HELP vaccine.
|
| 巻・号 |
163(1)
|
| ページ |
102-12
|
| 公開日 |
2015-1-1
|
| DOI |
10.1016/j.imlet.2014.11.016
|
| PII |
S0165-2478(14)00295-8
|
| PMID |
25479286
|
| MeSH |
Adjuvants, Immunologic / pharmacology*
Animals
Cancer Vaccines / chemistry
Cancer Vaccines / immunology*
Cell Line, Tumor
Dendritic Cells / immunology
Dendritic Cells / pathology
Epitopes, T-Lymphocyte / chemistry
Epitopes, T-Lymphocyte / immunology
Epitopes, T-Lymphocyte / pharmacology*
Humans
Immunity, Cellular / drug effects
Mice
Neoplasms, Experimental / drug therapy*
Neoplasms, Experimental / immunology
Neoplasms, Experimental / pathology
Oligodeoxyribonucleotides / pharmacology*
Peptides / chemical synthesis
Peptides / chemistry
Peptides / immunology
Peptides / pharmacology*
Th1 Cells / immunology
Th1 Cells / pathology
|
| IF |
3.276
|
| 引用数 |
5
|
|
WOS 分野
|
IMMUNOLOGY
|
| リソース情報 |
| 実験動物マウス |
RBRC00144 |
