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Titolo:
Activation of innate immunity in nonhuman primates following intraportal administration of adenoviral vectors
Autore:
Schnell, MA; Zhang, Y; Tazelaar, J; Gao, GP; Yu, QC; Qian, R; Chen, SJ; Varnavski, AN; LeClair, C; Raper, SE; Wilson, JM;
Indirizzi:
Univ Penn, Inst Human Gene Therapy, Philadelphia, PA 19104 USA Univ Penn Philadelphia PA USA 19104 e Therapy, Philadelphia, PA 19104 USA Univ Penn, Dept Mol & Cellular Engn, Philadelphia, PA 19104 USA Univ PennPhiladelphia PA USA 19104 ular Engn, Philadelphia, PA 19104 USA Univ Penn, Dept Surg, Philadelphia, PA 19104 USA Univ Penn Philadelphia PA USA 19104 Dept Surg, Philadelphia, PA 19104 USA
Titolo Testata:
MOLECULAR THERAPY
fascicolo: 5, volume: 3, anno: 2001,
parte:, 1
pagine: 708 - 722
SICI:
1525-0016(200105)3:5<708:AOIIIN>2.0.ZU;2-C
Fonte:
ISI
Lingua:
ENG
Soggetto:
MEDIATED GENE-TRANSFER; CONDUCTANCE REGULATOR CDNA; DENDRITIC CELLS; RECOMBINANT ADENOVIRUSES; IN-VIVO; TRANSGENE EXPRESSION; RHESUS-MONKEY; LYMPH-NODES; MOUSE-LIVER; THERAPY;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
47
Recensione:
Indirizzi per estratti:
Indirizzo: Wilson, JM 204 Wistar Inst, 3601 Spruce St, Philadelphia, PA 19104 USA 204Wistar Inst 3601 Spruce St Philadelphia PA USA 19104 04 USA
Citazione:
M.A. Schnell et al., "Activation of innate immunity in nonhuman primates following intraportal administration of adenoviral vectors", MOL THER, 3(5), 2001, pp. 708-722

Abstract

The innate immune response to intraportally infused adenoviral vector was evaluated in rhesus monkeys. A first-generation adenovirus-expressing lacZ (Ad-lacZ) was administered at a dose just below that which causes severe morbidity. The response to vector was evaluated for the initial 24 h following infusion. Clinical findings during this time were primarily limited to petechiae, consistent with the development of thrombocytopenia and biochemical evidence of disseminated intravascular coagulation. Serum transaminases were elevated and a lymphopenia developed. Tracking of fluorescent-labeled vector demonstrated distribution to macrophages and dendritic cells of the spleen and Kupffer cells of the liver. A systemic release of the cytokine IL-6 occurred soon after vector infusion. Analysis of splenic cells revealed acute activation of macrophages and dendritic cells followed by massive apoptosis. Bone marrow cultures demonstrated normal erythroid and primitive progenitors with a significant decrease in myeloid progenitors. Similar findings, except the abnormality in bone marrow cultures, were observed in monkeys who received an identical dose of Ad-lacZ in which vector genes were inactivated with psoralen and UV irradiation. These data suggest that inadvertent targeting of antigen-presenting cells following intraportal infusion ofvector leads to a systemic cytokine syndrome which may be triggered by theviral capsid proteins.

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Documento generato il 26/01/20 alle ore 22:17:47