Catalogo Articoli (Spogli Riviste)

OPAC HELP

Titolo:
Circumventing tolerance to a human MDM2-derived tumor antigen by TCR gene transfer
Autore:
Stanislawski, T; Voss, RH; Lotz, C; Sadovnikova, E; Willemsen, RA; Kuball, J; Ruppert, T; Bolhuis, RLH; Melief, CJ; Huber, C; Stauss, HJ; Theobald, M;
Indirizzi:
Univ Mainz, Dept Hematol & Oncol, D-55101 Mainz, Germany Univ Mainz Mainz Germany D-55101 Hematol & Oncol, D-55101 Mainz, Germany Hammersmith Hosp, Imperial Coll Sch Med, Dept Immunol, London W12 0NN, England Hammersmith Hosp London England W12 0NN Immunol, London W12 0NN, England Dr Daniel Den Hoed Canc Ctr, Dept Clin & Tumor Immunol, NL-3075 EA Rotterdam, Netherlands Dr Daniel Den Hoed Canc Ctr Rotterdam Netherlands NL-3075EA Netherlands Univ Munich, Max Von Pettenkofer Inst Virol, D-80336 Munich, Germany Univ Munich Munich Germany D-80336 r Inst Virol, D-80336 Munich, Germany Leiden Univ, Med Ctr, Dept Immunohematol & Blood Transfus, NL-2333 ZA Leiden, Netherlands Leiden Univ Leiden Netherlands NL-2333 ZA NL-2333 ZA Leiden, Netherlands
Titolo Testata:
NATURE IMMUNOLOGY
fascicolo: 10, volume: 2, anno: 2001,
pagine: 962 - 970
SICI:
1529-2908(200110)2:10<962:CTTAHM>2.0.ZU;2-6
Fonte:
ISI
Lingua:
ENG
Soggetto:
CLASS-I MOLECULES; CYTOTOXIC T-LYMPHOCYTES; DENDRITIC CELLS; HIGH-AFFINITY; P53 PROTEIN; MHC; PEPTIDE; IMMUNOTHERAPY; PROTEASOME; RECEPTOR;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
44
Recensione:
Indirizzi per estratti:
Indirizzo: Theobald, M Univ Mainz, Dept Hematol & Oncol, D-55101 Mainz, Germany Univ Mainz Mainz Germany D-55101 col, D-55101 Mainz, Germany
Citazione:
T. Stanislawski et al., "Circumventing tolerance to a human MDM2-derived tumor antigen by TCR gene transfer", NAT IMMUNOL, 2(10), 2001, pp. 962-970

Abstract

We identified a tumor-associated cytotoxic T lymphocyte (CTL) epitope derived from the widely expressed human MDM2 oncoprotein and were able to bypass self-tolerance to this tumor antigen in HLA-A*0201 (A2.1) transgenic miceand by generating A2.1-negative, allo-A2.1-restricted human T lymphocytes. A broad range of malignant, as opposed to nontransformed cells, were killed by high-avidity transgenic mouse and allogeneic human CTLs specific for the A2.1-presented MDM2 epitope. Whereas the self-A2.1-restricted human T cell repertoire gave rise only to low-avidity CTLs unable to recognize the natural MDM2 peptide, human A2.1(+) T lymphocytes were turned into efficient MDM2-specific CTLs upon expression of wild-type and partially humanized high-affinity T cell antigen receptor (TCR) genes derived from the transgenic mice. These results demonstrate that TCR gene transfer can be used to circumvent self-tolerance of autologous T lymphocytes to universal tumor antigens and thus provide the basis for a TCR gene transfer-based broad-spectrum immunotherapy of malignant disease.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 24/01/20 alle ore 12:30:27