title: Differential lysis of tumors by polyclonal T cell lines and T cell clones specific for hTERT.
abstract: The human telomerase reverse transcriptase hTERT is overexpressed in most human tumors and contributes importantly to oncogenesis by maintaining the integrity of telomeric DNA. Despite being a self-antigen, the hTERT enzyme is immunogenic. Peptides derived from hTERT have been shown both in vitro and in vivo to drive the activation and proliferation of peptide-specific T lymphocytes. An HLA-A2-binding peptide from Htert (I540, ILAKFLHWL) has been used to generate peptide-specific T cells in vitro and in vivo in patients that lyse telomerase-positive tumors in an MHC-restricted fashion. Although these and other data suggest that I540 is naturally processed and presented on the surface of certain tumor cells, there are reports that I540-specific T cells, and in particular, T cell clones, do not lyse tumors in vitro. Here, we compared cytotoxic function of I540-specfic T cell clones vs. polyclonal T cell lines, including clones and lines generated from the same donor. We found that I540-specific polyclonal T cell lines lyse telomerase-positive tumors whereas non-specific polyclonal T cell lines and I540-specific T cell clones do not. Estimated TCR avidity for I540, as well as cell surface expression of CD45RO, CD45RA, CD28, CD27, CD57 and CD62L were similar between lines and clones. V beta usage, however, differed such that the majority of the I540-specific TCR repertoire found in polyclonal T cell lines was not represented in clones generated from the same source material. Thus, I540-specific T cells can vary in cytotoxic potential depending on the method of generation, isolation and expansion.
authors: Abramson Family Cancer Research Institute, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA.
authors: Dih-Yih
authors: DY
authors: Chen
authors: Barbara A
authors: BA
authors: Vance
authors: Lara B S
authors: LB
authors: Thompson
authors: Susan M
authors: SM
authors: Domchek
authors: Robert H
authors: RH
authors: Vonderheide
mesh_terms: D015703:Antigens, CD / Q000032:analysis; D000951:Antigens, Neoplasm / Q000032:analysis; D019496:Cancer Vaccines / Q000276:immunology; D045744:Cell Line, Tumor / Q000276:immunology; D002999:Clone Cells / Q000276:immunology; D003602:Cytotoxicity, Immunologic; D003713:Dendritic Cells / Q000276:immunology; D015333:Gene Rearrangement, beta-Chain T-Cell Antigen Receptor; D015789:HLA-A2 Antigen / Q000276:immunology; D006801:Humans; D016056:Immunodominant Epitopes / Q000276:immunology; D020014:K562 Cells / Q000276:immunology / Q000528:radiation effects; D009363:Neoplasm Proteins / Q000276:immunology*; D010446:Peptide Fragments / Q000276:immunology*; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics / Q000276:immunology*; D037182:T-Cell Antigen Receptor Specificity; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D019098:Telomerase / Q000276:immunology*
chemical_list: D015703:Antigens, CD; D000951:Antigens, Neoplasm; D019496:Cancer Vaccines; D015789:HLA-A2 Antigen; D016056:Immunodominant Epitopes; D009363:Neoplasm Proteins; D010446:Peptide Fragments; D016693:Receptors, Antigen, T-Cell, alpha-beta; C437311:telomerase reverse transcriptase (540-548); C509186:TERT protein, human; D019098:Telomerase