Induction of tumor-reactive cytotoxic T-lymphocytes using a peptide from NY-ESO-1 modified at the carboxy-terminus to enhance HLA-A2.1 binding affinity and stability in solution

S. Bownds, P. Tong-On, S. A. Rosenberg, M. Parkhurst

Research output: Contribution to journalArticle

Abstract

NY-ESO-1 is an attractive candidate tumor antigen for the development of immunotherapies for a wide variety of cancers. It is expressed in multiple types of tumors, but its normal tissue distribution is predominantly limited to the testes and ovaries; furthermore, both humoral and cellular immune responses can be mounted against this protein. Three overlapping HLA-A2.1-restricted T-cell epitopes have been identified within NY-ESO-1. In this investigation, the authors evaluated the in vitro immunogenicity of these peptides. From 2 of 12 HLA-A2.1+ patients with metastatic melanoma, peptide-reactive cytotoxic T-lymphocytes were generated using either NY-ESO-1:157-167 or NY-ESO-l:157-165 but not NY-ESO-l:155-163. Because NY-ESO-1:157-165 is a 9 amino acid peptide completely contained within NY-ESO-1:157-167, it seemed likely that this peptide was the minimal determinant, and thus it was selected for continued study. An amino acid substitution of C to V was introduced into NY-ESO-1:157-165 at P9 to attempt to improve its immunogenicity by enhancing its binding affinity to HLA-A2.1 and increasing its stability in solution, because the C residue is readily oxidized, leading to dimerization of the peptide. From 5 of 20 HLA-A2.1+ patients with metastatic melanoma, NY-ESO-1:157-165(165V) stimulated cytotoxic T-lymphocytes in vitro, which recognized peptide-pulsed target cells and HLA-A2.1+ NY-ESO-1+ tumor cells, suggesting that this peptide may be clinically valuable for the treatment of patients with NY-ESO-1+ tumors.

Original languageEnglish (US)
Pages (from-to)1-9
Number of pages9
JournalJournal of Immunotherapy
Volume24
Issue number1
DOIs
StatePublished - Feb 7 2001

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Keywords

  • Cancer testis antigens
  • Cytotoxic T lymphocytes
  • Epitope
  • HLA-A2.1
  • Immunotherapy
  • NY-ESO-1

ASJC Scopus subject areas

  • Immunology
  • Pharmacology
  • Cancer Research

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