A long, naturally presented immunodominant epitope from NY-ESO-1 tumor antigen: implications for cancer vaccine design

Lisa M Ebert, Yu Chih Liu, Craig Steven Clements, Neil C Robson, Heather M Jackson, Jessica L Markby, Nektaria Dimopoulos, Bee Shin Tan, Immanuel F Luescher, Ian D Davis, Jamie Rossjohn, Jonathan Cebon, Anthony Wayne Purcell, Weisan Chen

Research output: Contribution to journalArticleResearchpeer-review

42 Citations (Scopus)

Abstract

The tumor antigen NY-ESO-1 is a promising cancer vaccine target. We describe here a novel HLA-B7-restricted NY-ESO-1 epitope, encompassing amino acids 60-72 (APRGPHGGAASGL), which is naturally presented by melanoma cells. The tumor epitope bound to HLA-B7 by bulging outward from the peptide-binding cleft. This bulged epitope was not an impediment to T-cell recognition, however, because four of six HLA-B7(+) melanoma patients vaccinated with NY-ESO-1 ISCOMATRIX vaccine generated a potent T-cell response to this determinant. Moreover, the response to this epitope was immunodominant in three of these patients and, unlike the T-cell responses to bulged HLA class I viral epitopes, the responding T cells possessed a remarkably broad TCR repertoire. Interestingly, HLA-B7(+) melanoma patients who did not receive the NY-ESO-1 ISCOMATRIX vaccine rarely generated a spontaneous T-cell response to this cryptic epitope, suggesting a lack of priming of such T cells in the natural anti-NY-ESO-1 response, which may be corrected by vaccination. Together, our results reveal several surprising aspects of antitumor immunity and have implications for cancer vaccine design. [Cancer Res 2009;69(3):1046-54].
Original languageEnglish
Pages (from-to)1046 - 1054
Number of pages9
JournalCancer Research
Volume69
Issue number3
DOIs
Publication statusPublished - 2009

Cite this

Ebert, L. M., Liu, Y. C., Clements, C. S., Robson, N. C., Jackson, H. M., Markby, J. L., ... Chen, W. (2009). A long, naturally presented immunodominant epitope from NY-ESO-1 tumor antigen: implications for cancer vaccine design. Cancer Research, 69(3), 1046 - 1054. https://doi.org/10.1158/0008-5472.CAN-08-2926
Ebert, Lisa M ; Liu, Yu Chih ; Clements, Craig Steven ; Robson, Neil C ; Jackson, Heather M ; Markby, Jessica L ; Dimopoulos, Nektaria ; Tan, Bee Shin ; Luescher, Immanuel F ; Davis, Ian D ; Rossjohn, Jamie ; Cebon, Jonathan ; Purcell, Anthony Wayne ; Chen, Weisan. / A long, naturally presented immunodominant epitope from NY-ESO-1 tumor antigen: implications for cancer vaccine design. In: Cancer Research. 2009 ; Vol. 69, No. 3. pp. 1046 - 1054.
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title = "A long, naturally presented immunodominant epitope from NY-ESO-1 tumor antigen: implications for cancer vaccine design",
abstract = "The tumor antigen NY-ESO-1 is a promising cancer vaccine target. We describe here a novel HLA-B7-restricted NY-ESO-1 epitope, encompassing amino acids 60-72 (APRGPHGGAASGL), which is naturally presented by melanoma cells. The tumor epitope bound to HLA-B7 by bulging outward from the peptide-binding cleft. This bulged epitope was not an impediment to T-cell recognition, however, because four of six HLA-B7(+) melanoma patients vaccinated with NY-ESO-1 ISCOMATRIX vaccine generated a potent T-cell response to this determinant. Moreover, the response to this epitope was immunodominant in three of these patients and, unlike the T-cell responses to bulged HLA class I viral epitopes, the responding T cells possessed a remarkably broad TCR repertoire. Interestingly, HLA-B7(+) melanoma patients who did not receive the NY-ESO-1 ISCOMATRIX vaccine rarely generated a spontaneous T-cell response to this cryptic epitope, suggesting a lack of priming of such T cells in the natural anti-NY-ESO-1 response, which may be corrected by vaccination. Together, our results reveal several surprising aspects of antitumor immunity and have implications for cancer vaccine design. [Cancer Res 2009;69(3):1046-54].",
author = "Ebert, {Lisa M} and Liu, {Yu Chih} and Clements, {Craig Steven} and Robson, {Neil C} and Jackson, {Heather M} and Markby, {Jessica L} and Nektaria Dimopoulos and Tan, {Bee Shin} and Luescher, {Immanuel F} and Davis, {Ian D} and Jamie Rossjohn and Jonathan Cebon and Purcell, {Anthony Wayne} and Weisan Chen",
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Ebert, LM, Liu, YC, Clements, CS, Robson, NC, Jackson, HM, Markby, JL, Dimopoulos, N, Tan, BS, Luescher, IF, Davis, ID, Rossjohn, J, Cebon, J, Purcell, AW & Chen, W 2009, 'A long, naturally presented immunodominant epitope from NY-ESO-1 tumor antigen: implications for cancer vaccine design', Cancer Research, vol. 69, no. 3, pp. 1046 - 1054. https://doi.org/10.1158/0008-5472.CAN-08-2926

A long, naturally presented immunodominant epitope from NY-ESO-1 tumor antigen: implications for cancer vaccine design. / Ebert, Lisa M; Liu, Yu Chih; Clements, Craig Steven; Robson, Neil C; Jackson, Heather M; Markby, Jessica L; Dimopoulos, Nektaria; Tan, Bee Shin; Luescher, Immanuel F; Davis, Ian D; Rossjohn, Jamie; Cebon, Jonathan; Purcell, Anthony Wayne; Chen, Weisan.

In: Cancer Research, Vol. 69, No. 3, 2009, p. 1046 - 1054.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - A long, naturally presented immunodominant epitope from NY-ESO-1 tumor antigen: implications for cancer vaccine design

AU - Ebert, Lisa M

AU - Liu, Yu Chih

AU - Clements, Craig Steven

AU - Robson, Neil C

AU - Jackson, Heather M

AU - Markby, Jessica L

AU - Dimopoulos, Nektaria

AU - Tan, Bee Shin

AU - Luescher, Immanuel F

AU - Davis, Ian D

AU - Rossjohn, Jamie

AU - Cebon, Jonathan

AU - Purcell, Anthony Wayne

AU - Chen, Weisan

PY - 2009

Y1 - 2009

N2 - The tumor antigen NY-ESO-1 is a promising cancer vaccine target. We describe here a novel HLA-B7-restricted NY-ESO-1 epitope, encompassing amino acids 60-72 (APRGPHGGAASGL), which is naturally presented by melanoma cells. The tumor epitope bound to HLA-B7 by bulging outward from the peptide-binding cleft. This bulged epitope was not an impediment to T-cell recognition, however, because four of six HLA-B7(+) melanoma patients vaccinated with NY-ESO-1 ISCOMATRIX vaccine generated a potent T-cell response to this determinant. Moreover, the response to this epitope was immunodominant in three of these patients and, unlike the T-cell responses to bulged HLA class I viral epitopes, the responding T cells possessed a remarkably broad TCR repertoire. Interestingly, HLA-B7(+) melanoma patients who did not receive the NY-ESO-1 ISCOMATRIX vaccine rarely generated a spontaneous T-cell response to this cryptic epitope, suggesting a lack of priming of such T cells in the natural anti-NY-ESO-1 response, which may be corrected by vaccination. Together, our results reveal several surprising aspects of antitumor immunity and have implications for cancer vaccine design. [Cancer Res 2009;69(3):1046-54].

AB - The tumor antigen NY-ESO-1 is a promising cancer vaccine target. We describe here a novel HLA-B7-restricted NY-ESO-1 epitope, encompassing amino acids 60-72 (APRGPHGGAASGL), which is naturally presented by melanoma cells. The tumor epitope bound to HLA-B7 by bulging outward from the peptide-binding cleft. This bulged epitope was not an impediment to T-cell recognition, however, because four of six HLA-B7(+) melanoma patients vaccinated with NY-ESO-1 ISCOMATRIX vaccine generated a potent T-cell response to this determinant. Moreover, the response to this epitope was immunodominant in three of these patients and, unlike the T-cell responses to bulged HLA class I viral epitopes, the responding T cells possessed a remarkably broad TCR repertoire. Interestingly, HLA-B7(+) melanoma patients who did not receive the NY-ESO-1 ISCOMATRIX vaccine rarely generated a spontaneous T-cell response to this cryptic epitope, suggesting a lack of priming of such T cells in the natural anti-NY-ESO-1 response, which may be corrected by vaccination. Together, our results reveal several surprising aspects of antitumor immunity and have implications for cancer vaccine design. [Cancer Res 2009;69(3):1046-54].

UR - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=19176376

U2 - 10.1158/0008-5472.CAN-08-2926

DO - 10.1158/0008-5472.CAN-08-2926

M3 - Article

VL - 69

SP - 1046

EP - 1054

JO - Cancer Research

JF - Cancer Research

SN - 0008-5472

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ER -