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
[11]   Telomerase vaccination has no detectable effect on SCID-repopulating and colony-forming activities in the bone marrow of cancer patients [J].
Danet-Desnoyers, GAH ;
Luongo, JL ;
Bonnet, DA ;
Domchek, SM ;
Vonderheide, RH .
EXPERIMENTAL HEMATOLOGY, 2005, 33 (11) :1275-1280
[12]  
DOMCHEK SM, 2006, P AM ASSOC CANC RES, pS4003
[13]  
Dudley ME, 2002, SCIENCE, V298, P850, DOI 10.1126/science.1076514
[14]   Artificial antigen-presenting cells transduced with telomerase efficiently expand epitope-specific, human leukocyte antigen-restricted cytotoxic T cells [J].
Dupont, J ;
Latouche, JB ;
Ma, C ;
Sadelain, N .
CANCER RESEARCH, 2005, 65 (12) :5417-5427
[15]   Frequency of telomerase-specific CD8+ T lymphocytes in patients with cancer [J].
Filaci, G ;
Fravega, M ;
Setti, M ;
Traverso, P ;
Millo, E ;
Fenoglio, D ;
Negrini, S ;
Ferrera, F ;
Romagnoli, A ;
Basso, M ;
Contini, P ;
Rizzi, M ;
Ghio, M ;
Benatti, U ;
Damonte, G ;
Ravetti, JL ;
Carmignani, G ;
Zanetti, M ;
Indiveri, F .
BLOOD, 2006, 107 (04) :1505-1512
[16]   Dendritic cells reconstituted with human telomerase gene induce potent cytotoxic T-cell response against different types of tumors [J].
Frolkis, M ;
Fischer, MB ;
Wang, Z ;
Lebkowski, JS ;
Chiu, CP ;
Majumdar, AS .
CANCER GENE THERAPY, 2003, 10 (03) :239-249
[17]   Ex vivo characterization of multiepitopic tumor-specific CD8 T cells in patients with chronic myeloid leukemia:: Implications for vaccine development and adoptive cellular immunotherapy [J].
Gannagé, M ;
Abel, M ;
Michallet, AS ;
Delluc, S ;
Lambert, M ;
Giraudier, S ;
Kratzer, R ;
Niedermann, G ;
Saveanu, L ;
Guilhot, F ;
Camoin, L ;
Varet, B ;
Buzyn, A ;
Caillat-Zucman, S .
JOURNAL OF IMMUNOLOGY, 2005, 174 (12) :8210-8218
[18]   High vaccination efficiency of low-affinity epitopes in antitumor immunotherapy [J].
Gross, DA ;
Graff-Dubois, S ;
Opolon, P ;
Cornet, S ;
Alves, P ;
Bennaceur-Griscelli, A ;
Faure, O ;
Guillaume, P ;
Firat, M ;
Chouaib, S ;
Lemonnier, FA ;
Davoust, J ;
Miconnet, I ;
Vonderheide, RH ;
Kosmatopoulos, K .
JOURNAL OF CLINICAL INVESTIGATION, 2004, 113 (03) :425-433
[19]   Inhibition of telomerase limits the growth of human cancer cells [J].
Hahn, WC ;
Stewart, SA ;
Brooks, MW ;
York, SG ;
Eaton, E ;
Kurachi, A ;
Beijersbergen, RL ;
Knoll, JHM ;
Meyerson, M ;
Weinberg, RA .
NATURE MEDICINE, 1999, 5 (10) :1164-1170
[20]   Telomerase activation, cellular immortalization and cancer [J].
Hahn, WC ;
Meyerson, M .
ANNALS OF MEDICINE, 2001, 33 (02) :123-129