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
in English
| 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.
Full text:
Available
Index:
LILACS (Americas)
Main subject:
Genetic Therapy
/
Leukemia
/
X-Linked Combined Immunodeficiency Diseases
Type of study:
Etiology study
/
Risk factors
Limits:
Humans
Language:
English
Journal:
Braz. j. med. biol. res
Journal subject:
Biology
/
Medicine
Year:
2007
Type:
Article
/
Project document
Affiliation country:
Brazil
Institution/Affiliation country:
Universidade de São Paulo/BR
Similar
MEDLINE
...
LILACS
LIS