Characterization of HLA-A3-restricted cytotoxic T lymphocytes reactive against the widely expressed tumor antigen telomerase

Robert H. Vonderheide, Karen S. Anderson, William C. Hahn, Mark O. Butler, Joachim L. Schultze, Lee M. Nadler

Research output: Contribution to journalArticle

95 Scopus citations

Abstract

Purpose: We have reported previously that the telomerase catalytic subunit, human telomerase reverse transcriptase (hTERT), is a widely expressed tumor-associated antigen recognized by CTLs. A nine-amino acid peptide derived from hTERT binds strongly to HLA-A2 antigen and elicits CTL responses against a broad panel of hTERT+ tumors (but not hTERT+ hematopoietic progenitor cells). The applicability of hTERT as a potential target for anticancer immunotherapy would be widened by the identification of epitopes restricted to other common HLA alleles, such as HLA-A3 antigen. Experimental Design: Using a method of epitope deduction, HLA-A3-restricted peptide epitopes were screened from hTERT and tested for immunogenicity in a human in vitro T-cell system. Results: The hTERT peptide K973 was used to generate specific CD8+ CTLs from HLA-A3+ cancer patients and healthy individuals. These CTLs lysed hTERT+ tumors from multiple histologies in an MHC-restricted fashion, suggesting that the epitope is naturally processed and presented by tumors. In contrast, highly enriched HLA-A3+ CD34+ peripheral blood progenitor cells or activated T cells were not lysed.

Original languageEnglish (US)
Pages (from-to)3343-3348
Number of pages6
JournalClinical Cancer Research
Volume7
Issue number11
StatePublished - Jan 1 2001
Externally publishedYes

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Vonderheide, R. H., Anderson, K. S., Hahn, W. C., Butler, M. O., Schultze, J. L., & Nadler, L. M. (2001). Characterization of HLA-A3-restricted cytotoxic T lymphocytes reactive against the widely expressed tumor antigen telomerase. Clinical Cancer Research, 7(11), 3343-3348.