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Review
. 2021 Aug 2;13(8):1528.
doi: 10.3390/v13081528.

Lentiviral Vectors for T Cell Engineering: Clinical Applications, Bioprocessing and Future Perspectives

Roman P Labbé  1   2 , Sandrine Vessillier  2 , Qasim A Rafiq  1
Affiliations
Review

Lentiviral Vectors for T Cell Engineering: Clinical Applications, Bioprocessing and Future Perspectives

Roman P Labbé et al. Viruses. .

Abstract

Lentiviral vectors have played a critical role in the emergence of gene-modified cell therapies, specifically T cell therapies. Tisagenlecleucel (Kymriah), axicabtagene ciloleucel (Yescarta) and most recently brexucabtagene autoleucel (Tecartus) are examples of T cell therapies which are now commercially available for distribution after successfully obtaining EMA and FDA approval for the treatment of blood cancers. All three therapies rely on retroviral vectors to transduce the therapeutic chimeric antigen receptor (CAR) into T lymphocytes. Although these innovations represent promising new therapeutic avenues, major obstacles remain in making them readily available tools for medical care. This article reviews the biological principles as well as the bioprocessing of lentiviral (LV) vectors and adoptive T cell therapy. Clinical and engineering successes, shortcomings and future opportunities are also discussed. The development of Good Manufacturing Practice (GMP)-compliant instruments, technologies and protocols will play an essential role in the development of LV-engineered T cell therapies.

Keywords: CAR; T cell; bioprocessing; lentivirus; manufacture; viral vector.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
The three generations of LV plasmid systems. Each Generation of LV vector is presented with the plasmid constructs necessary for its production and with the genes each plasmid carries.
Figure 1
Figure 1
The three generations of LV plasmid systems. Each Generation of LV vector is presented with the plasmid constructs necessary for its production and with the genes each plasmid carries.
Figure 2
Figure 2
Example of an end-to-end upstream and downstream bioprocess for GMP-grade LV vector production. This figure describes the bioprocess patented by Oxford Biomedica (Oxford, UK) for the production of their GMP-grade lentiviral vector using their suspension-adapted, serum-free HEK293T producer cell line. This process includes an inducible plasmid system dependent on sodium butyrate. Each batch is individually cryopreserved and stored until enough material is produced, to then be combined, filtered and concentrated for final formulation [14,45,46].
Figure 3
Figure 3
Viral vector and autologous CAR T cell therapy bioprocessing.
See this image and copyright information in PMC

References

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    1. European Medicines Agency. Committee for Medicinal Products for Human Use. Committee for Medicinal Products for Human Use (CHMP) Summary of Positive Opinion Kymriah. 2018.

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