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Review
. 2005 Jan;16(1):17-25.
doi: 10.1089/hum.2005.16.17.

Regulatory considerations for novel gene therapy products: a review of the process leading to the first clinical lentiviral vector

Peter Manilla  1 , Tessio Rebello, Cathleen Afable, Xiaobin Lu, Vladimir Slepushkin, Laurent M Humeau, Kathy Schonely, Yajin Ni, Gwendolyn K Binder, Bruce L Levine, Rob-Roy MacGregor, Carl H June, Boro Dropulic
Affiliations
Review

Regulatory considerations for novel gene therapy products: a review of the process leading to the first clinical lentiviral vector

Peter Manilla et al. Hum Gene Ther. 2005 Jan.

Erratum in

  • Hum Gene Ther. 2005 Feb;16(2):279
  • Hum Gene Ther. 2006 Feb;17(2):252

Abstract

This review is intended to exemplify the roles and responsibilities of the two agencies under the Department of Health and Human Services, the National Institutes of Health and the Food and Drug Administration, that have oversight for human gene transfer clinical protocols, as seen through our experience of bringing a first-in-its-class lentiviral vector to clinical trials. In response to the changing circumstances in gene therapy research between 1999 and 2002, the concerns of these agencies regarding gene therapy have been evolving. This review provides an overview of the major safety concerns regarding insertional oncogenesis, the generation of a replication- competent lentivirus (RCL), and vector mobilization thought to be related to lentiviral vectors, which had to be addressed during the regulatory review process before initiating the clinical trial. Specific monitoring assays to address these concerns were established to test for RCL generation, vector mobilization, persistence of vector-modified cells, and abnormal clonal expansion of modified cells. We hope to provide a basic understanding and appreciation of the regulatory process and major safety concerns, toward providing useful insight to those presently embarking on the development of clinical application of lentiviral vectors.

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