A Long, Naturally Presented Immunodominant Epitope from NY-ESO-1 Tumor Antigen: Implications for Cancer Vaccine Design Academic Article uri icon

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.

authors

  • 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

publication date

  • February 1, 2009

has subject area