Telomerase-based immunotherapy of cancer

被引:24
作者
Carpenter, Erica L. [1 ]
Vonderheide, Robert H. [1 ]
机构
[1] Univ Penn, Sch Med, Abramson Family Canc Res Inst, Philadelphia, PA 19104 USA
关键词
cancer; cytotoxic T lymphocyte; hTERT; immunotherapy; T cell; telomerase; telomerase reverse transcriptase;
D O I
10.1517/14712598.6.10.1031
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 ; 0836 ; 090102 ; 100705 ;
摘要
The progression from the cloning of human telomerase reverse transcriptase.(hTERT) in 1997 to the first clinical trials of hTERT as an antitumour immunotherapy target has been swift. hTERT is overexpressed in the vast majority of human cancers yet has limited expression in normal adult tissue. it plays a critical role in oncogenesis and may be expressed by cancer stem cells. However, despite being a self antigen, hTERT is immunogenic both in vitro and in vivo. Several Phase I studies of hTERT immunotherapy have been completed in patients with breast, prostate, lung and other cancers, and clinical and immunological results are encouraging. Immunotherapy induces functional, antitumour T cells in patients in the absence of clinical toxicity. The opportunity for vaccinating individuals as an immunoprevention strategy can also be envisioned for hTERT-based therapies.
引用
收藏
页码:1031 / 1039
页数:9
相关论文
共 60 条
[1]   Immunogenic HLA-B*0702-restricted epitopes derived from human telomerase reverse transcriptase that elicit antitumor cytotoxic T-cell responses [J].
Adotevi, Olivier ;
Mollier, Karine ;
Neuveut, Christine ;
Cardinaud, Sylvain ;
Boulanger, Emmanuelle ;
Mignen, Blandine ;
Fridman, Wolf-Herve ;
Zanetti, Maurizio ;
Charneau, Pierre ;
Tartour, Eric ;
Lemonnier, Frangois ;
Langlade-Demoyen, Pierre .
CLINICAL CANCER RESEARCH, 2006, 12 (10) :3158-3167
[2]   Identification of human telomerase reverse transcriptase-derived peptides that induce HLA-A24-restricted antileukemia cytotoxic T lymphocytes [J].
Arai, J ;
Yasukawa, M ;
Ohminami, H ;
Kakimoto, M ;
Hasegawa, A ;
Fujita, S .
BLOOD, 2001, 97 (09) :2903-2907
[3]  
Ayyoub M, 2001, EUR J IMMUNOL, V31, P2642, DOI 10.1002/1521-4141(200109)31:9<2642::AID-IMMU2642>3.0.CO
[4]  
2-6
[5]   Switching and signaling at the telomere [J].
Blackburn, EH .
CELL, 2001, 106 (06) :661-673
[6]   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
[7]   Telomerase peptide vaccination: a phase I/II study in patients with non-small cell lung cancer [J].
Brunsvig, Paal F. ;
Aamdal, Steinar ;
Gjertsen, Marianne K. ;
Kvalheim, Gunnar ;
Markowski-Grimsrud, Carrie J. ;
Sve, Ingunn ;
Dyrhaug, Marianne ;
Trachsel, Sissel ;
Moller, Mona ;
Eriksen, Jon A. ;
Gaudernack, Gustav .
CANCER IMMUNOLOGY IMMUNOTHERAPY, 2006, 55 (12) :1553-1564
[8]   Human telomerase and its regulation [J].
Cong, YS ;
Wright, WE ;
Shay, JW .
MICROBIOLOGY AND MOLECULAR BIOLOGY REVIEWS, 2002, 66 (03) :407-+
[9]   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
[10]   Dissociation between stem cell phenotype and NOD/SCID repopulating activity in human peripheral blood CD34+ cells after ex vivo expansion [J].
Danet, GH ;
Lee, HW ;
Luongo, JL ;
Simon, MC ;
Bonnet, DA .
EXPERIMENTAL HEMATOLOGY, 2001, 29 (12) :1465-1473