Replication competent retrovirus testing (RCR) in the National Gene Vector Biorepository: No evidence of RCR in 1,595 post-treatment peripheral blood samples obtained from 60 clinical trials Journal Article

   

Authors:	Cornetta, K.; Yao, J.; House, K.; Duffy, L.; Adusumilli, P. S.; Beyer, R.; Booth, C.; Brenner, M.; Curran, K.; Grilley, B.; Heslop, H.; Hinrichs, C. S.; Kaplan, R. N.; Kiem, H. P.; Kochenderfer, J.; Kohn, D. B.; Mailankody, S.; Norberg, S. M.; O'Cearbhaill, R. E.; Pappas, J.; Park, J.; Ramos, C.; Ribas, A.; Rivière, I.; Rosenberg, S. A.; Sauter, C.; Shah, N. N.; Slovin, S. F.; Thrasher, A.; Williams, D. A.; Lin, T. Y.
Article Title:	Replication competent retrovirus testing (RCR) in the National Gene Vector Biorepository: No evidence of RCR in 1,595 post-treatment peripheral blood samples obtained from 60 clinical trials
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. © 2022 The Author(s)
Keywords:	adult; controlled study; human tissue; human cell; major clinical study; genetics; nonhuman; cancer immunotherapy; cell line; patient monitoring; gene vector; genetic vectors; blood sampling; gene therapy; safety; virus replication; retroviridae; adverse event; genetic therapy; humans; human; male; female; article; biobank; rolling circle replication; replication competent retrovirus
Journal Title:	Molecular Therapy
Volume:	31
Issue:	3
ISSN:	1525-0016
Publisher:	Nature Publishing Group
Date Published:	2023-03-01
Start Page:	801
End Page:	809
Language:	English
DOI:	10.1016/j.ymthe.2022.12.006
PUBMED:	36518078
PROVIDER:	scopus
PMCID:	PMC10014217
DOI/URL:	https://www.scopus.com/inward/record.uri?eid=2-s2.0-85147107979&doi=10.1016%2fj.ymthe.2022.12.006&partnerID=40&md5=8640b179a6054967a3f750eac80416b5
Notes:	Article -- MSK Cancer Center Support Grant (P30 CA008748) acknowledged in PubMed and PDF -- Source: Scopus

https://synapse.mskcc.org/synapse/works/has_related_data_chk/204536