Gene therapy clinical trials worldwide 1989–2004—an overview

Abstract

In 1989, Rosenberg et al. performed the first human gene therapy trial when they used a retrovirus to introduce the gene coding for resistance to neomycin into human tumor-infiltrating lymphocytes before infusing them into five patients with advanced melanoma. This study demonstrated the feasibility of using retroviral gene transduction in humans and set the stage for further studies. Since then, over 900 clinical trials have been completed, are ongoing or have been approved worldwide. These trials have been designed to establish feasibility and safety, to demonstrate the reality of expression of therapeutic protein(s) in vivo by the genes transferred and, in some cases, to show therapeutic benefit. There is no single source of information that presents an overview of all the clinical trials undertaken worldwide. In 1997 we set up a database to bring all the information on clinical trials together as comprehensively and as globally as possible. The data were compiled and are regularly updated from official agency sources, the published literature, presentations at conferences and from information kindly provided by investigators or trial sponsors themselves. As of January 31, 2004, we have identified 918 trials in 24 countries. The USA accounts for two-thirds of these trials. Cancer is by far the most common disease indication, followed by inherited monogenic diseases, and cardiovascular diseases. Viral vectors have been the most frequently used vehicles for transferring genes into human cells, with retroviruses and adenoviruses representing the vast majority. Plasmid (naked) DNA and other non-viral vectors have been used in one-quarter of the trials. Over 100 distinct genes have been transferred. This article aims to provide a descriptive overview of the clinical trials that, to the best of our knowledge, have been or are being performed worldwide. Details of the data presented, including an interactive, searchable database that currently holds information on 918 trials, can be found on The Journal of Gene Medicine clinical trials website 1.

Novel degradable oligoethylenimine acrylate ester-based pseudodendrimers for in vitro and in vivo gene transfer

“…1 Nonviral gene carriers might be advantageous due to pharmaceutical issues, such as low cost of synthesis and easy scale-up, but they show poor transfection efficiency levels in comparison to their viral counterparts. 2,3 Thus, an excellent in vivo transfection activity at low toxicity should be the major considerations regarding the design of novel nonviral gene delivery devices.…”

Therapeutic targeting in the silent era: advances in non-viral siRNA delivery

“…Moreover, the potential for mutagenesis may also cause unexpected consequences to the host [12] . Clinical trials involving non-viral-vector based gene therapies have dramatically increased from 2004 to 2007, while the number of viral vector trials is steadily dropping over the same period [49,50] . Thus, we will focus our attention for the remaining part of this review on the significant advances and improvements in non-viral delivery technologies and how they can be applied to siRNA-based therapeutics.…”

Osteosarcoma: Current status of immunotherapy and future trends (Review)

“…The most investigated gene transfer vector is the adenoviral vector (Adv) (69). A single injection of Advencoding IL-2 gene (Ad IL-2) into a primary tumor lesion elicited anti-tumoral immunity and this immunity not only suppressed primary tumor growth but also eradicated disseminated micro-metastases in distant organs (70).…”