Abstract
The cancer-testis antigen NY-ESO-1 has been implicated as one of the most attractive candidates for a cancer vaccine. However, a protein vaccine generally meets inefficient antigen presentation to CD8+ T cells, which could be overcome by combination with an appropriate adjuvant. Heat shock protein is a natural adjuvant and activates the antigen-presenting cells to channel exogenous antigens into the classical major histocompatibility complex class I antigen-processing pathway (cross-presentation). Therefore, we genetically fused a minigene encompassing the NY-ESO-1 cytotoxic T lymphocyte (CTL) epitope 157-165 (ESO p157-165) to the human heat shock cognate protein 70 (hsc70) and expressed the resulting fusion proteins in Escherichia coli. By using a human leukocyte antigen-A*0201-restricted NY-ESO-1-specific CTL clone, the cross-presentation of ESO p157-165 by monocyte-derived dendritic cells (mo-DC) pulsed with the fusion protein was evaluated. The fusion protein-pulsed mo-DC activates the CTL clone much more efficiently than the free NY-ESO-1 protein-pulsed mo-DC. Moreover, the magnitude of the CTL activity was comparable between ESO p157-165 and the fusion protein of hsc70 and ESO p157-165 (hsc70-ESO p157-165 fusion protein). In addition, the CTL activation induced by the fusion protein, but not by the epitope, was inhibited by paraformaldehyde fixation of the mo-DC and by treatment with lactacystin, a specific inhibitor for the proteasome. Finally, the hsc70-ESO p157-165 fusion protein-pulsed DC was able to induce an antigen-specific T-cell response. These results suggest that the hsc70-ESO p157-165 fusion protein is therefore considered to be a promising candidate as a cancer vaccine.
| Original language | English |
|---|---|
| Pages (from-to) | 107-112 |
| Number of pages | 6 |
| Journal | Cancer Science |
| Volume | 99 |
| Issue number | 1 |
| DOIs | |
| Publication status | Published - Jan 2008 |
| Externally published | Yes |
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ASJC Scopus subject areas
- Cancer Research
- Oncology
Cite this
Cross-presentation of NY-ESO-1 cytotoxic T lymphocyte epitope fused to human heat shock cognate protein 70 by dendritic cells. / Susumu, Seiya; Nagata, Yasuhiro; Ito, Shinichiro; Matsuo, Mitsutoshi; Valmori, Danila; Yui, Katsuyuki; Udono, Heiichiro; Kanematsu, Takashi.
In: Cancer Science, Vol. 99, No. 1, 01.2008, p. 107-112.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Cross-presentation of NY-ESO-1 cytotoxic T lymphocyte epitope fused to human heat shock cognate protein 70 by dendritic cells
AU - Susumu, Seiya
AU - Nagata, Yasuhiro
AU - Ito, Shinichiro
AU - Matsuo, Mitsutoshi
AU - Valmori, Danila
AU - Yui, Katsuyuki
AU - Udono, Heiichiro
AU - Kanematsu, Takashi
PY - 2008/1
Y1 - 2008/1
N2 - The cancer-testis antigen NY-ESO-1 has been implicated as one of the most attractive candidates for a cancer vaccine. However, a protein vaccine generally meets inefficient antigen presentation to CD8+ T cells, which could be overcome by combination with an appropriate adjuvant. Heat shock protein is a natural adjuvant and activates the antigen-presenting cells to channel exogenous antigens into the classical major histocompatibility complex class I antigen-processing pathway (cross-presentation). Therefore, we genetically fused a minigene encompassing the NY-ESO-1 cytotoxic T lymphocyte (CTL) epitope 157-165 (ESO p157-165) to the human heat shock cognate protein 70 (hsc70) and expressed the resulting fusion proteins in Escherichia coli. By using a human leukocyte antigen-A*0201-restricted NY-ESO-1-specific CTL clone, the cross-presentation of ESO p157-165 by monocyte-derived dendritic cells (mo-DC) pulsed with the fusion protein was evaluated. The fusion protein-pulsed mo-DC activates the CTL clone much more efficiently than the free NY-ESO-1 protein-pulsed mo-DC. Moreover, the magnitude of the CTL activity was comparable between ESO p157-165 and the fusion protein of hsc70 and ESO p157-165 (hsc70-ESO p157-165 fusion protein). In addition, the CTL activation induced by the fusion protein, but not by the epitope, was inhibited by paraformaldehyde fixation of the mo-DC and by treatment with lactacystin, a specific inhibitor for the proteasome. Finally, the hsc70-ESO p157-165 fusion protein-pulsed DC was able to induce an antigen-specific T-cell response. These results suggest that the hsc70-ESO p157-165 fusion protein is therefore considered to be a promising candidate as a cancer vaccine.
AB - The cancer-testis antigen NY-ESO-1 has been implicated as one of the most attractive candidates for a cancer vaccine. However, a protein vaccine generally meets inefficient antigen presentation to CD8+ T cells, which could be overcome by combination with an appropriate adjuvant. Heat shock protein is a natural adjuvant and activates the antigen-presenting cells to channel exogenous antigens into the classical major histocompatibility complex class I antigen-processing pathway (cross-presentation). Therefore, we genetically fused a minigene encompassing the NY-ESO-1 cytotoxic T lymphocyte (CTL) epitope 157-165 (ESO p157-165) to the human heat shock cognate protein 70 (hsc70) and expressed the resulting fusion proteins in Escherichia coli. By using a human leukocyte antigen-A*0201-restricted NY-ESO-1-specific CTL clone, the cross-presentation of ESO p157-165 by monocyte-derived dendritic cells (mo-DC) pulsed with the fusion protein was evaluated. The fusion protein-pulsed mo-DC activates the CTL clone much more efficiently than the free NY-ESO-1 protein-pulsed mo-DC. Moreover, the magnitude of the CTL activity was comparable between ESO p157-165 and the fusion protein of hsc70 and ESO p157-165 (hsc70-ESO p157-165 fusion protein). In addition, the CTL activation induced by the fusion protein, but not by the epitope, was inhibited by paraformaldehyde fixation of the mo-DC and by treatment with lactacystin, a specific inhibitor for the proteasome. Finally, the hsc70-ESO p157-165 fusion protein-pulsed DC was able to induce an antigen-specific T-cell response. These results suggest that the hsc70-ESO p157-165 fusion protein is therefore considered to be a promising candidate as a cancer vaccine.
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UR - http://www.scopus.com/inward/citedby.url?scp=36949020042&partnerID=8YFLogxK
U2 - 10.1111/j.1349-7006.2007.00654.x
DO - 10.1111/j.1349-7006.2007.00654.x
M3 - Article
C2 - 17991294
AN - SCOPUS:36949020042
VL - 99
SP - 107
EP - 112
JO - Cancer Science
JF - Cancer Science
SN - 1347-9032
IS - 1
ER -