Cancer Immunology, Immunotherapy

, Volume 53, Issue 7, pp 589–599

Identification of an antigenic peptide derived from the cancer-testis antigen NY-ESO-1 binding to a broad range of HLA-DR subtypes

  • Frank Neumann
  • Claudia Wagner
  • Boris Kubuschok
  • Stefan Stevanovic
  • Hans-Georg Rammensee
  • Michael Pfreundschuh
Original Article

DOI: 10.1007/s00262-003-0492-6

Cite this article as:
Neumann, F., Wagner, C., Kubuschok, B. et al. Cancer Immunol Immunother (2004) 53: 589. doi:10.1007/s00262-003-0492-6

Abstract

NY-ESO-1 is a SEREX-defined cancer-testis antigen of which several MHC I, but only few MHC II–restricted epitopes have been identified. Searching for highly promiscuous MHC II–restricted peptides that might be suitable as a CD4+ stimulating vaccine for many patients, we used the SYFPEITHI algorithm and identified an NY-ESO-1–derived pentadecamer epitope (p134–148) that induced specific CD4+ T-cell responses restricted to the HLA-DRB1 subtypes *0101, *0301, *0401, and *0701 that have a cumulative prevalence of 40% in the Caucasian population. The DR restriction of the p134–148 pentadecamer was demonstrated by inhibition with an HLA-DR antibody and a functional peptide displacement titration assay with the pan-DR-binding T-helper epitope PADRE as the competitor. The natural processing and presentation of this epitope was demonstrated by recognition of an NY-ESO-1+ melanoma cell line by T cells with specificity for p134–148. The pentadecamer p134–148 was able to induce CD4+ responses in 4/38 cancer patients tested. However, no strict correlation was found between CD4+ T-cell responses against p134–148 reactivity and anti-NY-ESO-1 antibody titers in the serum of patients, suggesting that CD4+ and B-cell responses are regulated independently. In conclusion, p134–148 holds promise as a broadly applicable peptide vaccine for patients with NY-ESO-1–positive neoplasms.

Keywords

T lymphocytesAntigenic peptide epitopesMHC IITumor immunityVaccination

Abbreviations

°C

degree Celsius

CD

cluster of differentiation

CTA

cancer-testis antigen

DC

dendritic cells

Gy

gray

mM

millimolar

ng

nanogram

PADRE

pan-DR-binding T-helper epitope

pp65

phosphoprotein 65

SSP-PCR

sequence-specific primer PCR

v/v

volume per volume

Copyright information

© Springer-Verlag 2004

Authors and Affiliations

  • Frank Neumann
    • 1
  • Claudia Wagner
    • 1
  • Boris Kubuschok
    • 1
  • Stefan Stevanovic
    • 2
  • Hans-Georg Rammensee
    • 2
  • Michael Pfreundschuh
    • 1
  1. 1.Med. Klinik ISaarland University Medical SchoolHomburgGermany
  2. 2.Institute for Cell Biology, Department of ImmunologyEberhard-Karls-UniversitätTübingenGermany