The telomerase catalytic subunit is a widely expressed tumor-associated antigen recognized by cytotoxic T lymphocytes

被引:493
作者
Vonderheide, RH [1 ]
Hahn, WC
Schultze, JL
Nadler, LM
机构
[1] Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA
[2] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA
[3] Whitehead Inst Biomed Res, Cambridge, MA 02142 USA
关键词
D O I
10.1016/S1074-7613(00)80066-7
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
The discovery of tumor-associated antigens (TAA) in certain human malignancies has prompted renewed efforts to develop antigen-specific immunotherapy of cancer. However, most TAA described thus far are expressed in one or a few tumor types, and, among patients with these types of tumors, TAA expression is not universal. Here, we characterize the telomerase catalytic subunit (hTERT) as a widely expressed TAA capable of triggering antitumor cytotoxic T lymphocyte (CTL) responses. More than 85% of human cancers exhibit strong telomerase activity, but normal adult tissues, with few exceptions, do not. In a human system, CD8(+) CTL specific for an hTERT peptide and restricted to MHC HLA-A2 lysed hTERT(+) tumors from multiple histologies. These findings identify hTERT as a potentially important and widely applicable target for anticancer immunotherapeutic strategies.
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收藏
页码:673 / 679
页数:7
相关论文
共 34 条
[1]   Extension of life-span by introduction of telomerase into normal human cells [J].
Bodnar, AG ;
Ouellette, M ;
Frolkis, M ;
Holt, SE ;
Chiu, CP ;
Morin, GB ;
Harley, CB ;
Shay, JW ;
Lichtsteiner, S ;
Wright, WE .
SCIENCE, 1998, 279 (5349) :349-352
[2]   Evidence for an alternative mechanism for maintaining telomere length in human tumors and tumor-derived cell lines [J].
Bryan, TM ;
Englezou, A ;
DallaPozza, L ;
Dunham, MA ;
Reddel, RR .
NATURE MEDICINE, 1997, 3 (11) :1271-1274
[3]  
BYSTRYN JC, 1992, CANCER RES, V52, P5948
[4]   Dissociation among in vitro telomerase activity, telomere maintenance, and cellular immortalization [J].
Counter, CM ;
Hahn, WC ;
Wei, WY ;
Caddle, SD ;
Beijersbergen, RL ;
Lansdorp, PM ;
Sedivy, JM ;
Weinberg, RA .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1998, 95 (25) :14723-14728
[5]   Telomerase activity is restored in human cells by ectopic expression of hTERT (hEST2), the catalytic subunit of telomerase [J].
Counter, CM ;
Meyerson, M ;
Eaton, EN ;
Ellisen, LW ;
Caddle, SD ;
Haber, DA ;
Weinberg, RA .
ONCOGENE, 1998, 16 (09) :1217-1222
[6]   TELOMERE SHORTENING ASSOCIATED WITH CHROMOSOME INSTABILITY IS ARRESTED IN IMMORTAL CELLS WHICH EXPRESS TELOMERASE ACTIVITY [J].
COUNTER, CM ;
AVILION, AA ;
LEFEUVRE, CE ;
STEWART, NG ;
GREIDER, CW ;
HARLEY, CB ;
BACCHETTI, S .
EMBO JOURNAL, 1992, 11 (05) :1921-1929
[7]   STABILIZATION OF SHORT TELOMERES AND TELOMERASE ACTIVITY ACCOMPANY IMMORTALIZATION OF EPSTEIN-BARR VIRUS-TRANSFORMED HUMAN B-LYMPHOCYTES [J].
COUNTER, CM ;
BOTELHO, FM ;
WANG, P ;
HARLEY, CB ;
BACCHETTI, S .
JOURNAL OF VIROLOGY, 1994, 68 (05) :3410-3414
[8]  
Fujie T, 1997, CLIN CANCER RES, V3, P2425
[9]  
GREIDER CW, 1995, TELOMERES, P35
[10]   Telomerase activity in the regenerative basal layer of the epidermis in human skin and in immortal and carcinoma-derived skin keratinocytes [J].
HarleBachor, C ;
Boukamp, P .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1996, 93 (13) :6476-6481