Combating oncogene activation associated with retrovirus-mediated gene therapy of X-linked severe combined immunodeficiency
Braz. j. med. biol. res
;
40(5): 601-613, May 2007. ilus, tab
Article
Dans Anglais
| LILACS
| ID: lil-449078
ABSTRACT
A successful gene therapy clinical trial that also encountered serious adverse effects has sparked extensive study and debate about the future directions for retrovirus-mediated interventions. Treatment of X-linked severe combined immunodeficiency with an oncoretrovirus harboring a normal copy of the gc gene was applied in two clinical trials, essentially curing 13 of 16 infants, restoring a normal immune system without the need for additional immune-related therapies. Approximately 3 years after their gene therapy, tragically, 3 of these children, all from the same trial, developed leukemia as a result of this experimental treatment. The current understanding of the mechanism behind this leukemogenesis involves three critical and cooperating factors, i.e., viral integration, oncogene activation, and the function of the therapeutic gene. In this review, we will explore the causes of this unwanted event and some of the possibilities for reducing the risk of its reoccurrence.
Texte intégral:
Disponible
Indice:
LILAS (Amériques)
Sujet Principal:
Thérapie génétique
/
Leucémies
/
Immunodéficiences combinées graves liées à l'X
Type d'étude:
Etude d'étiologie
/
Facteurs de risque
Limites du sujet:
Humains
langue:
Anglais
Texte intégral:
Braz. j. med. biol. res
Thème du journal:
Biologie
/
Médicament
Année:
2007
Type:
Article
/
descriptif de projet
Pays d'affiliation:
Brésil
Institution/Pays d'affiliation:
Universidade de São Paulo/BR
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