Large-scale clinical-grade retroviral vector production in a fixed-bed bioreactor

Journal of Immunotherapy
Xiuyan WangIsabelle Rivière

Abstract

The successful genetic engineering of patient T cells with γ-retroviral vectors expressing chimeric antigen receptors or T-cell receptors for phase II clinical trials and beyond requires the large-scale manufacture of high-titer vector stocks. The production of retroviral vectors from stable packaging cell lines using roller bottles or 10- to 40-layer cell factories is limited by a narrow harvest window, labor intensity, open-system operations, and the requirement for significant incubator space. To circumvent these shortcomings, we optimized the production of vector stocks in a disposable fixed-bed bioreactor using good manufacturing practice-grade packaging cell lines. High-titer vector stocks were harvested over 10 days, representing a much broader harvest window than the 3-day harvest afforded by cell factories. For PG13 and 293Vec packaging cells, the average vector titer and the vector stocks' yield in the bioreactor were higher by 3.2- to 7.3-fold, and 5.6- to 13.1-fold, respectively, than those obtained in cell factories. The vector production was 10.4 and 18.6 times more efficient than in cell factories for PG13 and 293Vec cells, respectively. Furthermore, the vectors produced from the fixed-bed bioreactors passed the ...Continue Reading

References

Sep 22, 2012·Current Opinion in Immunology·Julia D SuerthChristopher Baum

❮ Previous
Next ❯

Citations

Nov 1, 2015·Human Molecular Genetics·Johannes C M van der Loo, J Fraser Wright
Jun 6, 2016·International Journal of Hematology·Marco L Davila, Michel Sadelain
Jun 28, 2016·Molecular Therapy Oncolytics·Xiuyan Wang, Isabelle Rivière
Oct 27, 2016·Journal of Biotechnology·Alexandra McCarronDavid Parsons
Nov 28, 2019·Expert Opinion on Biological Therapy·Mafalda G MoleirinhoCristina Peixoto
May 31, 2020·Cells·Chiara F MagnaniGiuseppe Gaipa
Sep 2, 2015·The Journal of Clinical Investigation·Michel Sadelain
Apr 19, 2017·Nature Nanotechnology·Tyrel T SmithMatthias T Stephan
May 16, 2019·Human Gene Therapy Methods·Alexandra McCarronDavid Parsons
Jun 20, 2019·Frontiers in Bioengineering and Biotechnology·Hasan UludagAysha Ansari
Apr 15, 2018·Leukemia·Michael C Milone, Una O'Doherty
Feb 23, 2020·Human Gene Therapy·Hanna M LeinonenHanna P Lesch
Aug 23, 2017·Human Gene Therapy Methods·Aziza P ManceurSven Ansorge
Sep 25, 2020·Biotechnology Journal·Hanna P LeschMinna Karhinen
Oct 5, 2019·Molecular Cancer Therapeutics·Jinsheng HanJianhui Cai
Feb 13, 2021·Viruses·Christopher Perry, Andrea C M E Rayat

❮ Previous
Next ❯

Methods Mentioned

BETA
PCA
FACS
PCR

Software Mentioned

JUMO PCA

Related Concepts

Related Feeds

Bioreactors (ASM)

Bioreactors are important devices or systems that utilize living cells or enzymes for a chemical process. These devices carefully control and monitor the environment factors such as pH, nutrients level, and temperature, which can affect the yield in a given process. Discover the latest research here.