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

Kenneth Cornetta; Jing Yao; Kimberley House; Lisa Duffy; Prasad S. Adusumilli; Rachel Beyer; Claire Booth; Malcolm Brenner; Kevin Curran; Bambi Grilley; Helen Heslop; Christian S. Hinrichs; Rosandra N. Kaplan; Hans Peter Kiem; James N. Kochenderfer; Donald B. Kohn; Sham Mailankody; Scott M. Norberg; Roisin E. O'Cearbhaill; Jennifer Pappas; Jae Park; Carlos Ramos; Antonio Ribas; Isabelle Rivière; Steven A. Rosenberg; Craig Sauter; Nirali N. Shah; Susan F. Slovin; Adrian Thrasher; David A. Williams; Tsai Yu Lin

doi:10.1016/j.ymthe.2022.12.006

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

Kenneth Cornetta, Jing Yao, Kimberley House, Lisa Duffy, Prasad S. Adusumilli, Rachel Beyer, Claire Booth, Malcolm Brenner, Kevin Curran, Bambi Grilley, Helen Heslop, Christian S. Hinrichs, Rosandra N. Kaplan, Hans Peter Kiem, James N. Kochenderfer, Donald B. Kohn, Sham Mailankody, Scott M. Norberg, Roisin E. O'Cearbhaill, Jennifer PappasJae Park, Carlos Ramos, Antonio Ribas, Isabelle Rivière, Steven A. Rosenberg, Craig Sauter, Nirali N. Shah, Susan F. Slovin, Adrian Thrasher, David A. Williams, Tsai Yu Lin

Research output: Contribution to journal › Article › peer-review

3 Scopus citations

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.

Original language	English (US)
Pages (from-to)	801-809
Number of pages	9
Journal	Molecular Therapy
Volume	31
Issue number	3
DOIs	https://doi.org/10.1016/j.ymthe.2022.12.006
State	Published - Mar 1 2023

Keywords

cancer immunotherapy
gene therapy
patient monitoring
replication competent retrovirus
safety
Cell Line
Virus Replication
Humans
Genetic Vectors/genetics
Genetic Therapy/adverse effects
Retroviridae/genetics

ASJC Scopus subject areas

Drug Discovery
Genetics
Molecular Medicine
Molecular Biology
Pharmacology

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10.1016/j.ymthe.2022.12.006

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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. N., Kohn, D. B., Mailankody, S., Norberg, S. M., O'Cearbhaill, R. E., ... Lin, T. Y. (2023). 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. Molecular Therapy, 31(3), 801-809. https://doi.org/10.1016/j.ymthe.2022.12.006

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. / Cornetta, Kenneth; Yao, Jing; House, Kimberley et al.
In: Molecular Therapy, Vol. 31, No. 3, 01.03.2023, p. 801-809.

Research output: Contribution to journal › Article › peer-review

Cornetta, K, Yao, J, House, K, Duffy, L, Adusumilli, PS, Beyer, R, Booth, C, Brenner, M, Curran, K, Grilley, B, Heslop, H, Hinrichs, CS, Kaplan, RN, Kiem, HP, Kochenderfer, JN, Kohn, DB, Mailankody, S, Norberg, SM, O'Cearbhaill, RE, Pappas, J, Park, J, Ramos, C, Ribas, A, Rivière, I, Rosenberg, SA, Sauter, C, Shah, NN, Slovin, SF, Thrasher, A, Williams, DA & Lin, TY 2023, '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', Molecular Therapy, vol. 31, no. 3, pp. 801-809. https://doi.org/10.1016/j.ymthe.2022.12.006

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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.",

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AU - Yao, Jing

AU - House, Kimberley

AU - Duffy, Lisa

AU - Adusumilli, Prasad S.

AU - Beyer, Rachel

AU - Booth, Claire

AU - Brenner, Malcolm

AU - Curran, Kevin

AU - Grilley, Bambi

AU - Heslop, Helen

AU - Hinrichs, Christian S.

AU - Kaplan, Rosandra N.

AU - Kiem, Hans Peter

AU - Kochenderfer, James N.

AU - Kohn, Donald B.

AU - Mailankody, Sham

AU - Norberg, Scott M.

AU - O'Cearbhaill, Roisin E.

AU - Pappas, Jennifer

AU - Park, Jae

AU - Ramos, Carlos

AU - Ribas, Antonio

AU - Rivière, Isabelle

AU - Rosenberg, Steven A.

AU - Sauter, Craig

AU - Shah, Nirali N.

AU - Slovin, Susan F.

AU - Thrasher, Adrian

AU - Williams, David A.

AU - Lin, Tsai Yu

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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

Keywords

ASJC Scopus subject areas

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