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

R. H. Vonderheide, Karen Anderson, W. C. Hahn, M. O. Butler, J. L. Schultze, L. M. Nadler

Research output: Contribution to journalArticle

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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 - 2001
Externally publishedYes

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HLA-A3 Antigen
Telomerase
Cytotoxic T-Lymphocytes
Neoplasm Antigens
Epitopes
Peptides
Neoplasms
T-Lymphocytes
HLA-A2 Antigen
human TERT protein
Hematopoietic Stem Cells
Immunotherapy
Blood Cells
Histology
Research Design
Stem Cells
Alleles
Amino Acids

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Vonderheide, R. H., Anderson, K., 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.

Characterization of HLA-A3-restricted cytotoxic T lymphocytes reactive against the widely expressed tumor antigen telomerase. / Vonderheide, R. H.; Anderson, Karen; Hahn, W. C.; Butler, M. O.; Schultze, J. L.; Nadler, L. M.

In: Clinical Cancer Research, Vol. 7, No. 11, 2001, p. 3343-3348.

Research output: Contribution to journalArticle

Vonderheide, R. H. ; Anderson, Karen ; Hahn, W. C. ; Butler, M. O. ; Schultze, J. L. ; Nadler, L. M. / Characterization of HLA-A3-restricted cytotoxic T lymphocytes reactive against the widely expressed tumor antigen telomerase. In: Clinical Cancer Research. 2001 ; Vol. 7, No. 11. pp. 3343-3348.
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