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. 2001 Nov;7(11):3343-8.

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

R H Vonderheide  1 , K S Anderson, W C Hahn, M O Butler, J L Schultze, L M Nadler
Affiliations
  • PMID: 11705846

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

R H Vonderheide et al. Clin Cancer Res. 2001 Nov.

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.

Conclusion: Given the expression of HLA-A2 and HLA-A3 antigen in the general population, these findings extend the potential applicability of hTERT as a therapeutic target to >60% of all cancer patients. The characterization of hTERT as a polyepitope, polyallelic tumor-associated antigen may provide an approach for circumventing therapy-induced resistance potentially mediated by antigenic- and allelic-loss tumor escape mutants.

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