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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.
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1 Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN 46202, USA
2 Surgery Branch, National Cancer Institute, Bethesda, MD 20892, USA; Stanford Cancer Institute, Stanford University, Stanford, CA 94305, USA
3 Stanford Cancer Institute, Stanford University, Stanford, CA 94305, USA
4 Department of Blood and Marrow Transplantation and Cellular Immunotherapy, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA
5 Department of Pediatrics, Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, New York, NY 10065, USA
6 Tufts Medical Center, Boston, MA 02111, USA
7 Department of Dermatology, Stanford University, Stanford, CA 94305, USA
8 Experimental Transplantation and Immunology Branch, National Cancer Institute, NIH, Bethesda, MD 20892, USA
9 Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, New York, NY 10021, USA
10 Department of Neurosurgery, Duke University Medical Center, Durham, NC 27710, USA
11 Fred Hutchinson Cancer Research Center and University of Washington School of Medicine, Seattle, WA 98109, USA
12 Pediatric Oncology Branch, National Cancer Institute, Bethesda, MD 20892, USA
13 Department of Medicine, Cellular Therapeutics Center, Center for Cell Engineering, and Molecular Pharmacology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA
14 Cell Therapy and Cell Engineering Facility, Center for Cell Engineering, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA
15 Surgery Branch, National Cancer Institute, Bethesda, MD 20892, USA