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Titolo:
In-vivo delivery of therapeutic proteins by genetically-modified cells: comparison of organoids and human serum albumin alginate-coated beads
Autore:
Shinya, E; Dervillez, X; Edwards-Levy, F; Duret, V; Brisson, E; Ylisastigui, L; Levy, MC; Cohen, JHM; Klatzmann, D;
Indirizzi:
Hop La Pitie Salpetriere, CERVI, Lab Biol & Therapeut Pathol Immunitaires,UPMC CNRS ESA 7087, F-75651 Paris 13, France Hop La Pitie Salpetriere Paris France 13 7087, F-75651 Paris 13, France CHU Robert Debre, Immunol Lab, F-51096 Reims, France CHU Robert Debre Reims France F-51096 Immunol Lab, F-51096 Reims, France Fac Pharm, UPRESA CNRS 1063, Lab Pharmacotech, F-51096 Reims, France Fac Pharm Reims France F-51096 , Lab Pharmacotech, F-51096 Reims, France
Titolo Testata:
BIOMEDICINE & PHARMACOTHERAPY
fascicolo: 10, volume: 53, anno: 1999,
pagine: 471 - 483
SICI:
0753-3322(199912)53:10<471:IDOTPB>2.0.ZU;2-V
Fonte:
ISI
Lingua:
ENG
Soggetto:
IMMUNODEFICIENCY-VIRUS TYPE-1; RECOMBINANT SOLUBLE CD4; AIDS-RELATED COMPLEX; HUMAN FACTOR-IX; ADENOASSOCIATED VIRUS; GENE-THERAPY; INTRAMUSCULAR INJECTION; BETA-THALASSEMIA; SUSTAINED EXPRESSION; IMMUNOCOMPETENT MICE;
Keywords:
gene therapy; HIV; multivalent;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
47
Recensione:
Indirizzi per estratti:
Indirizzo: Klatzmann, D Hop La Pitie Salpetriere, CERVI, Lab Biol & Therapeut Pathol Immunitaires,UPMC CNRS ESA 7087, 83 Blvd Hop, F-75651 Paris 13, France Hop La Pitie Salpetriere 83 Blvd Hop Paris France 13 France
Citazione:
E. Shinya et al., "In-vivo delivery of therapeutic proteins by genetically-modified cells: comparison of organoids and human serum albumin alginate-coated beads", BIOMED PHAR, 53(10), 1999, pp. 471-483

Abstract

We have designed a self-assembling multimeric soluble CD4 molecule by inserting the C-terminal fragment of the alpha chain of human C4-binding protein (C4bp alpha) at the C-terminal end of human soluble CD4 genes. This CD4-C4bp alpha fusion protein (sMulti-CD4) and two other reference molecules, a fusion protein of human serum albumin (HSA) and the first two domains of CD4 (HSA-CD4) and monomeric soluble CD4 (sMono-CD4), were delivered in vivo by genetically modified 293 cells. These cells were implanted in mice as organoids and also encapsulated in HSA alginate-coated beads. sMulti-CD4 showed an apparent molecular weight of about 300-350 kDa, in accordance with a possible heptamer formula. sMulti-CD4 produced either in cell culture or in vivo in mice appeared to be a better in-vitro inhibitor of HIV infection than sMono-CD4. Plasma levels of sMulti-CD4, HSA-CD4, and sMono-CD4 reached approximately 2,300, 2,700, and 170 ng/mL, respectively, 13 weeks after in-vivo organoid implantation, which had formed rumours at that rime. This suggests that the plasma half-life of sMulti-CD4 is much longer than that of sMono-CDL1. The 293 xenogeneic cells encapsulated in HSA alginate coated beads remained alive and kept secreting sMono-CD4 or HSA-CD4 continuously at significant levels for 18 weeks in nude mice, without tumour formation, When implanted in immunocompetent Balb/c mice, they were rejected two to three weeks after implantation. Zn contrast, encapsulated BL4 hybridoma cells remained alive and kept secreting BL4 anti-CD4, mAb for at least four weeks in Balb/c mice. These results suggest the clinical potential of the C4bp-multimerizing system, which could improve both the biological activity and the poor in-vivo pharmacokinetic performance of a monomeric functional protein like soluble CD4. These data also show that a systemic delivery of therapeutic proteins, including immunoglobulins, can be obtained by the in-vivo implantation of engineered allogeneic cells encapsulated in HSA alginate-coatedbeads. (C) 1999 Editions scientifiques et medicales Elsevier SAS.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 03/12/20 alle ore 15:14:59