Characterization of HLA-A3-restricted Cytotoxic T Lymphocytes Reactive against the Widely Expressed Tumor Antigen Telomerase

摘要: Purpose: We have reported previously that the telomerase catalytic subunit, human 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 and elicits CTL responses against broad panel of + tumors (but not hematopoietic progenitor cells). The applicability as potential target for anticancer immunotherapy would be widened identification epitopes restricted other common HLA alleles, such HLA-A3 antigen. Experimental Design: Using method epitope deduction, HLA-A3-restricted were screened tested immunogenicity in vitro T-cell system. Results: K973 was used generate specific CD8 CTLs cancer patients healthy individuals. These lysed multiple histologies an MHC-restricted fashion, suggesting naturally processed presented tumors. In contrast, highly enriched CD34 peripheral blood cells or activated T lysed. Conclusion: Given expression general population, these findings extend therapeutic >60% all patients. characterization polyepitope, polyallelic may provide approach circumventing therapy-induced resistance potentially mediated antigenic- allelic-loss tumor escape mutants.