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Titolo:
Therapeutic efficacy of OX-40 receptor antibody depends on tumor immunogenicity and anatomic site of tumor growth
Autore:
Kjaergaard, J; Tanaka, J; Kim, JA; Rothchild, K; Weinberg, A; Shu, SY;
Indirizzi:
Cleveland Clin Fdn, Surg Res Ctr, Cleveland, OH 44195 USA Cleveland Clin Fdn Cleveland OH USA 44195 es Ctr, Cleveland, OH 44195 USA Providence Portland Med Ctr, Earle A Chiles Res Inst, Portland, OR 97213 USA Providence Portland Med Ctr Portland OR USA 97213 Portland, OR 97213 USA
Titolo Testata:
CANCER RESEARCH
fascicolo: 19, volume: 60, anno: 2000,
pagine: 5514 - 5521
SICI:
0008-5472(20001001)60:19<5514:TEOORA>2.0.ZU;2-R
Fonte:
ISI
Lingua:
ENG
Soggetto:
T-CELL ACTIVATION; WILD-TYPE TUMOR; IN-VIVO; OX40 LIGAND; AUTOIMMUNE ENCEPHALOMYELITIS; TOLERANCE INDUCTION; B-16 MELANOMA; BRAIN-TUMORS; SPINAL-CORD; LEWIS RATS;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Life Sciences
Citazioni:
54
Recensione:
Indirizzi per estratti:
Indirizzo: Shu, SY Cleveland Clin Fdn, Surg Res Ctr, 9500 Euclid Ave,FF50, Cleveland,OH 44195 USA Cleveland Clin Fdn 9500 Euclid Ave,FF50 Cleveland OH USA 44195 USA
Citazione:
J. Kjaergaard et al., "Therapeutic efficacy of OX-40 receptor antibody depends on tumor immunogenicity and anatomic site of tumor growth", CANCER RES, 60(19), 2000, pp. 5514-5521

Abstract

The OX-40 receptor (OX-40R) is a cell surface glycoprotein of the tumor necrosis factor receptor family that is expressed primarily on activated CD4 T cells, Engagement of OX-40R by the OX-40 ligand (OX-40L) is known to costimulate the production of cytokines by activated T lymphocytes and to rescue effector T cells from activation-induced cell death, It was previously reported that in vivo ligation of OX-40R by administration of OX-40L:immunoglobulin fusion protein or OX-40R monoclonal antibody (mAb) resulted in a significant prolongation of survival of tumor-bearing mice in four histologically distinct solid tumors, In this study, we demonstrate that the therapeutic efficacy of OX-40R mAb was influenced by the tumor burden, the intrinsicimmunogenicity of the tumor as well as by the histological site of tumor growth. Whereas subdermal and intracranial growth of weakly immunogenic MCA 203 and MCA 205 sarcomas and GL261 glioma were susceptible to the mAb treatment, established pulmonary MCA 205 metastases were refractory to the same regimen of treatment. Furthermore, the mAb administration had no impact on the growth of the poorly immunogenic B16/D5 melanoma, Tumor regression mediated by OX-40R mAb was dependent on the participation of both CD4 and CD8 Tcells and as a result of tumor rejection, a long-term tumor-specific immunity was established. Analysis of tumor-infiltrating T cells revealed the presence of a far greater number of OX-40R(+) T cells of both CD4 and CDS phenotypes in the intracranial immunogenic GL261 glioma than that in the poorly immunogenic: B16/D5 melanoma, These results suggest that ligation of OX-40R on activated T cells in situ in the tumor may provide a necessary costimulatory signal to augment immune responses leading to tumor regression and immunological memory.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 12/07/20 alle ore 04:21:39