Center for Medical Ethics and Health Policy Staff Publications
Publication Date
3-1-2023
Journal
Molecular Therapy
DOI
10.1016/j.ymthe.2022.12.006
PMID
36518078
PMCID
PMC10014217
PubMedCentral® Posted Date
3-1-2023
PubMedCentral® Full Text Version
Post-print
Published Open-Access
yes
Keywords
Humans, Virus Replication, Retroviridae, Genetic Vectors, Cell Line, Genetic Therapy, cancer immunotherapy, gene therapy, patient monitoring, replication competent retrovirus, safety
Abstract
The clinical impact of any therapy requires the product be safe and effective. Gammaretroviral vectors pose several unique risks, including inadvertent exposure to replication competent retrovirus (RCR) that can arise during vector manufacture. The US FDA has required patient monitoring for RCR, and the National Gene Vector Biorepository is an NIH resource that has assisted eligible investigators in meeting this requirement. To date, we have found no evidence of RCR in 338 pre-treatment and 1,595 post-treatment blood samples from 737 patients associated with 60 clinical trials. Most samples (75%) were obtained within 1 year of treatment, and samples as far out as 9 years after treatment were analyzed. The majority of trials (93%) were cancer immunotherapy, and 90% of the trials used vector products produced with the PG13 packaging cell line. The data presented here provide further evidence that current manufacturing methods generate RCR-free products and support the overall safety profile of retroviral gene therapy.