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

被引：8

作者：

Cornetta, Kenneth ^{[1
,2
]}

Yao, Jing ^{[1
]}

House, Kimberley ^{[1
]}

Duffy, Lisa ^{[1
]}

Adusumilli, Prasad S. ^{[3
]}

Beyer, Rachel ^{[4
]}

Booth, Claire ^{[5
]}

Brenner, Malcolm ^{[6
]}

Curran, Kevin ^{[7
,8
]}

Grilley, Bambi ^{[6
]}

Heslop, Helen ^{[6
]}

Hinrichs, Christian S. ^{[9
,10
]}

Kaplan, Rosandra N. ^{[11
]}

Kiem, Hans-Peter ^{[12
,13
]}

Kochenderfer, James ^{[14
]}

Kohn, Donald B. ^{[15
,16
,17
]}

Mailankody, Sham ^{[18
]}

Norberg, Scott M. ^{[19
]}

O'Cearbhaill, Roisin E. ^{[3
]}

Pappas, Jennifer ^{[4
]}

Park, Jae ^{[3
]}

Ramos, Carlos ^{[6
]}

Ribas, Antonio ^{[20
]}

Riviere, Isabelle ^{[3
]}

Rosenberg, Steven A. ^{[4
]}

Sauter, Craig ^{[21
]}

Shah, Nirali N. ^{[11
]}

Slovin, Susan F. ^{[22
]}

Thrasher, Adrian ^{[5
]}

Williams, David A. ^{[23
]}

Lin, Tsai-Yu ^{[1
,2
]}

机构：

[1] Indiana Univ Sch Med, Dept Med & Mol Genet, Indianapolis, IN USA

[2] Indiana Univ Sch Med, Brown Ctr Immunotherapy, Indianapolis, IN USA

[3] Mem Sloan Kettering Canc Ctr, New York, NY USA

[4] NCI, Surg Branch, Bethesda, MD 20892 USA

[5] UCL Great Ormond St Inst Child Hlth, Mol & Cellular Immunol, London, England

[6] Baylor Coll Med, Ctr Cell & Gene Therapy, Houston, TX USA

[7] Mem Sloan Kettering Canc Ctr, Dept Pediat, New York, NY USA

[8] Weill Cornell Med Coll, Dept Pediat, New York, NY USA

[9] Duncan & Nancy MacMillan Canc Immunol & Metab Ctr, New Brunswick, NJ 08901 USA

[10] Rutgers Canc Inst New Jersey, New Brunswick, NJ 08901 USA

[11] NCI, Pediat Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA

[12] Fred Hutchison Canc Ctr, Seattle, WA USA

[13] Univ Washington, Seattle, WA USA

[14] NCI, Ctr Canc Res, Surg Branch, NIH, Bethesda, MD USA

[15] Univ Calif Los Angeles, Dept Microbiol Immunol & Mol Genet, Los Angeles, CA USA

[16] Univ Calif Los Angeles, Dept Pediat Hematol Oncol, Los Angeles, CA USA

[17] Univ Calif Los Angeles, Dept Mol & Med Pharmacol, Los Angeles, CA USA

[18] Mem Sloan Kettering Canc Ctr, Dept Med, Myeloma & Cellular Therapy Serv, New York, NY USA

[19] NCI, Ctr Immunooncol, Bethesda, MD 20892 USA

[20] Univ Calif Los Angeles, Jonsson Comprehens Canc Ctr, Los Angeles, CA 90095 USA

[21] Cleveland Clin, Taussig Canc Inst, Cleveland, OH USA

[22] Mem Sloan Kettering Canc Ctr, Sidney Kimmel Ctr Prostate & Urol Canc, Genitourinary Oncol Serv, New York, NY USA

[23] Harvard Med Sch, Boston Childrens Hosp, Boston, MA USA

来源：

MOLECULAR THERAPY | 2023年 / 31卷 / 03期

基金：

美国国家卫生研究院;

关键词：

THERAPY; VIRUS; CELLS;

D O I：

10.1016/j.ymthe.2022.12.006

中图分类号：

Q81 [生物工程学（生物技术）]; Q93 [微生物学];

学科分类号：

071005 ; 0836 ; 090102 ; 100705 ;

摘要：

The clinical impact of any therapy requires the product be safe and effective. Gammaretroviral vectors pose several unique risks, including inadvertent exposure to replication compe-tent retrovirus (RCR) that can arise during vector manufac-ture. 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 immuno-therapy, 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.

引用

页码：801 / 809

页数：9

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