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Evolution
of a Gene Therapy Clinical Trial
Laura
K. Aguilar¹,
Estuardo Aguilar-Cordova²
¹Harvard
Gene Therapy Initiative, Harvard Medical School, Boston, MA, USA;
²Advantagene, Inc., Waban, MA, USA
Developing
and conducting gene therapy clinical trials poses unique challenges which must
be addressed to satisfy regulatory requirements and, most importantly, to
protect human subjects.
Experimental products used for gene transfer studies, such as viral vectors, are
often complex and cannot be sterilized or completely characterized to the extent
of a typical pharmaceutical.
Thus, quality and characterization must be built into the production
process.
Extensive preclinical studies must be performed to determine the feasibility of
the approach, the safety of the product, and the appropriate dose range to
evaluate in humans.
Once a clinical trial is initiated, subjects must be followed carefully for
short- and long-term toxicity especially since preclinical studies may not
adequately predict the toxicity profile of these novel, complicated
products.
Results of early phase studies in gene therapy have often sent the investigators
back to the laboratory to improve the delivery vector or identify a more potent
or less toxic gene.
This circular developmental process is expected for the early stages of a new
technology such as gene therapy.
Although these hurdles appear extensive, they can be overcome, as evidenced by
the initiation of more than 500 clinical gene therapy trials in the United
States to date, and are imperative for the maintenance of high-quality studies
and public trust.
This article describes the step-by-step process for developing a gene therapy
trial incorporating specific examples relevant to neuro-oncology.
Keywords:
brain tumor, gene therapy, glioma, vector
Copyright
© 2003 Kluwer
Academic Publishers. All
rights reserved
Source: http://ipsapp009.kluweronline.com/content/getfile/5042/105/12/abstract.htm
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