Screening Clinical Cell Products for Replication Competent Retrovirus: The National Gene Vector Biorepository Experience

Kenneth Cornetta, Lisa Duffy, Steven A. Feldman, Crystal L. Mackall, Marco L. Davila, Kevin J. Curran, Richard P. Junghans, Jean Yuh Tang, James N. Kochenderfer, Roisin O'Cearbhaill, Gary Archer, Hans Peter Kiem, Nirali N. Shah, Cindy Delbrook, Rosie Kaplan, Renier J. Brentjens, Isabelle Rivière, Michel Sadelain, Steven A. Rosenberg

Research output: Contribution to journalArticlepeer-review

6 Scopus citations

Abstract

Replication-competent retrovirus (RCR) is a safety concern for individuals treated with retroviral gene therapy. RCR detection assays are used to detect RCR in manufactured vector, transduced cell products infused into research subjects, and in the research subjects after treatment. In this study, we reviewed 286 control (n = 4) and transduced cell products (n = 282) screened for RCR in the National Gene Vector Biorepository. The transduced cell samples were submitted from 14 clinical trials. All vector products were previously shown to be negative for RCR prior to use in cell transduction. After transduction, all 282 transduced cell products were negative for RCR. In addition, 241 of the clinical trial participants were also screened for RCR by analyzing peripheral blood at least 1 month after infusion, all of which were also negative for evidence of RCR infection. The majority of vector products used in the clinical trials were generated in the PG13 packaging cell line. The findings suggest that screening of the retroviral vector product generated in PG13 cell line may be sufficient and that further screening of transduced cells does not provide added value.

Original languageEnglish (US)
Pages (from-to)371-378
Number of pages8
JournalMolecular Therapy - Methods and Clinical Development
Volume10
DOIs
StatePublished - Sep 21 2018

Keywords

  • lentivirus
  • replicating virus
  • retrovirus
  • safety testing

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Genetics

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