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Titolo:
An immunomodulatory procedure that stabilizes transgene expression and permits readministration of E1-deleted adenovirus vectors
Autore:
Kuzmin, AI; Galenko, O; Eisensmith, RC;
Indirizzi:
CUNY Mt Sinai Sch Med, Inst Gene Therapy & Mol Med, New York, NY 10029 USACUNY Mt Sinai Sch Med New York NY USA 10029 l Med, New York, NY 10029 USA CUNY Mt Sinai Sch Med, Dept Human Genet, New York, NY 10029 USA CUNY Mt Sinai Sch Med New York NY USA 10029 Genet, New York, NY 10029 USA
Titolo Testata:
MOLECULAR THERAPY
fascicolo: 3, volume: 3, anno: 2001,
pagine: 293 - 301
SICI:
1525-0016(200103)3:3<293:AIPTST>2.0.ZU;2-N
Fonte:
ISI
Lingua:
ENG
Soggetto:
MEDIATED GENE-TRANSFER; ENCAPSULATED DICHLOROMETHYLENE DIPHOSPHONATE; CD40-CD40 LIGAND INTERACTIONS; CYTOTOXIC T-LYMPHOCYTES; IN-VIVO; CD40 LIGAND; RECOMBINANT ADENOVIRUS; IMMUNE-RESPONSES; B-CELLS; MACROPHAGE DEPLETION;
Keywords:
E1-deleted adenovirus vector; transgene; antibody; macrophage depletion; CD40L; gene therapy;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
47
Recensione:
Indirizzi per estratti:
Indirizzo: Eisensmith, RC CUNY Mt Sinai Sch Med, Inst Gene Therapy & Mol Med, 1 Gustave Pl,Box 1496,New York, NY 10029 USA CUNY Mt Sinai Sch Med 1 Gustave Pl,Box 1496 New York NY USA 10029
Citazione:
A.I. Kuzmin et al., "An immunomodulatory procedure that stabilizes transgene expression and permits readministration of E1-deleted adenovirus vectors", MOL THER, 3(3), 2001, pp. 293-301

Abstract

Immune responses against E1-deleted adenovirus vectors and/or their transgene products result in the rapid elimination of vector-transduced cells andthe generation of neutralizing antibodies. Different strategies of immunomodulation to stabilize transgene expression at therapeutic levels and to permit productive vector readministration have been examined. Our previous studies have shown that depletion of macrophages from spleen and liver decreases hepatic inflammation, significantly prolongs transgene expression, and delays the onset of humoral immune responses after systemic administration of an E1-deleted adenovirus vector. In the present study, we have examined the effects of macrophage depletion in combination with temporary blockade of CD40 ligation on E1-deleted adenovirus vector-mediated gene transfer. Alone, each of these treatments significantly inhibited the humoral immune response against the transgene product and prolonged its expression. Together, these treatments completely stabilized transgene expression and inhibitedthe production of neutralizing anti-adenovirus antibodies, permitting successful vector readministration. Animals rendered immunologically unresponsive to vector and transgene antigens regained their ability to mount productive immune responses against the vector after recovery of immune function, but remained unresponsive to the transgene product. These experiments demonstrate that this treatment is transient and antigen-specific.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 19/02/20 alle ore 15:34:13