Challenges in Vector and Trial Design Using Retroviral Vectors for Long-Term Gene Correction in Hematopoietic Stem Cell Gene Therapy

Research output: Other contribution

32 Citations (Scopus)

Abstract

Over the past two decades, incredible progress has been made using gene therapy for inherited severe immunodeficiency disorders, such as X-linked severe combined immunodeficiency disorder (SCID-X1) and adenosine deaminase deficiency–severe combined immunodeficiency disorder (ADA-SCID).1,2,3 However, for reasons that remain unclear, gene transfer for SCID-X1 has also been associated with some cases of vector-induced leukemia whereas no cases have been seen in the ADA-SCID trials despite the common use of g-retroviral vectors. The first case was reported in a French gene transfer trial for SCID-X1. Over the next six years, an additional three cases were reported in that trial and one in a second SCID-X1 trial that enrolled a combined total of 20 subjects. Unfortunately, genotoxicity would not remain confined to SCID-X1.
Original languageUnknown
Volume20
DOIs
Publication statusPublished - 1 Jan 2012

Cite this

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title = "Challenges in Vector and Trial Design Using Retroviral Vectors for Long-Term Gene Correction in Hematopoietic Stem Cell Gene Therapy",
abstract = "Over the past two decades, incredible progress has been made using gene therapy for inherited severe immunodeficiency disorders, such as X-linked severe combined immunodeficiency disorder (SCID-X1) and adenosine deaminase deficiency–severe combined immunodeficiency disorder (ADA-SCID).1,2,3 However, for reasons that remain unclear, gene transfer for SCID-X1 has also been associated with some cases of vector-induced leukemia whereas no cases have been seen in the ADA-SCID trials despite the common use of g-retroviral vectors. The first case was reported in a French gene transfer trial for SCID-X1. Over the next six years, an additional three cases were reported in that trial and one in a second SCID-X1 trial that enrolled a combined total of 20 subjects. Unfortunately, genotoxicity would not remain confined to SCID-X1.",
keywords = "BETA-THALASSEMIA, INTEGRATION SITES, IMMUNODEFICIENCY, LENTIVIRAL VECTOR, CHRONIC GRANULOMATOUS-DISEASE, INSERTIONAL ACTIVATION, MICE, PROGENITOR CELLS, CLINICAL-TRIALS, C-MYB",
author = "Carrondo, {Manuel Jos{\'e} Teixeira}",
year = "2012",
month = "1",
day = "1",
doi = "10.1038/mt.2012.93",
language = "Unknown",
volume = "20",
type = "Other",

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TY - GEN

T1 - Challenges in Vector and Trial Design Using Retroviral Vectors for Long-Term Gene Correction in Hematopoietic Stem Cell Gene Therapy

AU - Carrondo, Manuel José Teixeira

PY - 2012/1/1

Y1 - 2012/1/1

N2 - Over the past two decades, incredible progress has been made using gene therapy for inherited severe immunodeficiency disorders, such as X-linked severe combined immunodeficiency disorder (SCID-X1) and adenosine deaminase deficiency–severe combined immunodeficiency disorder (ADA-SCID).1,2,3 However, for reasons that remain unclear, gene transfer for SCID-X1 has also been associated with some cases of vector-induced leukemia whereas no cases have been seen in the ADA-SCID trials despite the common use of g-retroviral vectors. The first case was reported in a French gene transfer trial for SCID-X1. Over the next six years, an additional three cases were reported in that trial and one in a second SCID-X1 trial that enrolled a combined total of 20 subjects. Unfortunately, genotoxicity would not remain confined to SCID-X1.

AB - Over the past two decades, incredible progress has been made using gene therapy for inherited severe immunodeficiency disorders, such as X-linked severe combined immunodeficiency disorder (SCID-X1) and adenosine deaminase deficiency–severe combined immunodeficiency disorder (ADA-SCID).1,2,3 However, for reasons that remain unclear, gene transfer for SCID-X1 has also been associated with some cases of vector-induced leukemia whereas no cases have been seen in the ADA-SCID trials despite the common use of g-retroviral vectors. The first case was reported in a French gene transfer trial for SCID-X1. Over the next six years, an additional three cases were reported in that trial and one in a second SCID-X1 trial that enrolled a combined total of 20 subjects. Unfortunately, genotoxicity would not remain confined to SCID-X1.

KW - BETA-THALASSEMIA

KW - INTEGRATION SITES

KW - IMMUNODEFICIENCY

KW - LENTIVIRAL VECTOR

KW - CHRONIC GRANULOMATOUS-DISEASE

KW - INSERTIONAL ACTIVATION

KW - MICE

KW - PROGENITOR CELLS

KW - CLINICAL-TRIALS

KW - C-MYB

U2 - 10.1038/mt.2012.93

DO - 10.1038/mt.2012.93

M3 - Other contribution

VL - 20

ER -