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Titolo:
RETROVIRAL TRANSFER OF THE GLUCOCEREBROSIDASE GENE INTO CD34(-DISEASE- IN-VIVO DETECTION OF TRANSDUCED CELLS WITHOUT MYELOABLATION() CELLSFROM PATIENTS WITH GAUCHER)
Autore:
DUNBAR CE; KOHN DB; SCHIFFMANN R; BARTON NW; NOLTA JA; ESPLIN JA; PENSIERO M; LONG ZF; LOCKEY C; EMMONS RVB; CSIK S; LEITMAN S; KREBS CB; CARTER C; BRADY RO; KARLSSON S;
Indirizzi:
CHILDRENS HOSP LOS ANGELES,DIV RES IMMUNOL & BONE MARROW TRANSPLANTATLOS ANGELES CA 90027 CHILDRENS HOSP LOS ANGELES,DIV RES IMMUNOL & BONE MARROW TRANSPLANTATLOS ANGELES CA 90027 NHLBI,HEMATOL BRANCH,NIH BETHESDA MD 20892 NINCDS,DEV & METAB NEUROL BRANCH,NIH BETHESDA MD 20892 UNIV SO CALIF,SCH MED,NORRIS COTTON CANC CTR LOS ANGELES CA 90089 GENET THERAPY INC GAITHERSBURG MD 00000 NIH,CTR CLIN,DEPT TRANSFUS MED BETHESDA MD 20892 LUND UNIV S-22362 LUND SWEDEN
Titolo Testata:
Human gene therapy
fascicolo: 17, volume: 9, anno: 1998,
pagine: 2629 - 2640
SICI:
1043-0342(1998)9:17<2629:RTOTGG>2.0.ZU;2-4
Fonte:
ISI
Lingua:
ENG
Soggetto:
HEMATOPOIETIC STEM-CELLS; BONE-MARROW CELLS; MACROPHAGE-TARGETED GLUCOCEREBROSIDASE; LONG-TERM ENGRAFTMENT; PERIPHERAL-BLOOD; ADENOSINE-DEAMINASE; ENZYME DEFICIENCY; PROGENITOR CELLS; IN-VIVO; MEDIATED TRANSFER;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Science Citation Index Expanded
Science Citation Index Expanded
Citazioni:
52
Recensione:
Indirizzi per estratti:
Citazione:
C.E. Dunbar et al., "RETROVIRAL TRANSFER OF THE GLUCOCEREBROSIDASE GENE INTO CD34(-DISEASE- IN-VIVO DETECTION OF TRANSDUCED CELLS WITHOUT MYELOABLATION() CELLSFROM PATIENTS WITH GAUCHER)", Human gene therapy, 9(17), 1998, pp. 2629-2640

Abstract

Retroviral gene transfer of the glucocerebrosidase gene to hematopoietic progenitor and stem cells has shown promising results in animal models and corrected the enzyme deficiency in cells from Gaucher patients in vitro, Therefore, a clinical protocol was initiated to explore the safety and feasibility of retroviral transduction of peripheral blood (PB) or bone marrow (BM) CD34(+) cells with the G1Gc vector, This vector uses the viral LTR promoter to express the human glucocerebrosidase cDNA, Three adult patients have been entered with follow-up of 6-15months. Target cells were G-CSF-mobilized and CD34-enriched PB cells or CD34-enriched steady state BM cells, and were transduced ex vivo for 72 hr, Patient 1 had PB cells transduced in the presence of autologous stromal marrow cells. Patient 2 had PB cells transduced in the presence of autologous stroma, IL-3, IL-6, and SCF, Patient 3 had BM cellstransduced in the presence of autologous stroma, IL-3, IL-6, and SCF,At the end of transduction, the cells were collected and infused immediately without any preparative treatment of the patients. The transduction efficiency of the CD34(+) cells at the end of transduction was approximately 1, 10, and I for patients 1, 2, and 3, respectively, as estimated by semiquantitative PCR on bulk samples and PCR analysis of individual hematopoietic colonies, Gene marking in vivo was demonstrated in patients 2 and 3. Patient 2 had vector-positive PB granulocytes and mononuclear bone marrow cells at I month postinfusion and positive PB mononuclear cells at 2 and 3 months postinfusion, Patient 3 had a positive BM sample at 1 month postinfusion but was negative thereafter. These results indicate that gene-marked cells can engraft and persistfor at least 3 months postinfusion, even without myeloablation, However, the level of corrected cells (<0.02%) is too low to result in any clinical benefit, and glucocerebrosidase enzyme activity did not increase in any patient following infusion of transduced cells, Modifications of vector systems and transduction conditions, along with partial myeloablation to allow higher levels of engraftment, may be necessary to achieve beneficial levels of correction in patients with Gaucher disease.

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Documento generato il 07/07/20 alle ore 21:05:23