Long-term stability of clinical-grade lentiviral vectors for cell therapy

Abstract

The use of lentiviral vectors in cell and gene therapy is steadily increasing, both in commercial and investigational therapies. Although existing data increasingly support the usefulness and safety of clinical-grade lentiviral vectors used in cell manufacturing, comprehensive studies specifically addressing their long-term stability are currently lacking. This is significant considering the high cost of producing and testing GMP-grade vectors, the limited number of production facilities, and lengthy queue for production slots. Therefore, an extended shelf life is a critical attribute to justify the investment in large vector lots for investigational cell therapies. This study offers a thorough examination of essential stability attributes, including vector titer, transduction efficiency, and potency for a series of clinical-grade vector lots, each assessed at a minimum of 36 months following their date of manufacture. The 13 vector lots included in this study were used for cell product manufacturing in 16 different clinical trials, and at the time of the analysis had a maximum storage time at -80°C of up to 8 years. The results emphasize the long-term durability and efficacy of GMP-grade lentiviral vectors for use in ex vivo cell therapy manufacturing.

Keywords: cell therapy; lentiviral vector; potency; titer stability; transduction efficiency.

Graphical abstract

Figure 1

Clinical LV titers remain stable over time Thirteen clinical LV lots were titered in SupT1 cells as part of vector release testing and at subsequent time points following storage at −80°C to assess long-term titer stability. SupT1 titers are expressed as transduction units per milliliter (TU/mL).

Figure 2

Transduction efficiency in clinical cell products does not decrease over time The surface expression of each transgene expressed by the vector lot used for production of clinical cell therapy products was determined by flow cytometry. The transduction efficiency of each formulated product manufactured with a specific vector lot at a given MOI (MOI 1 [top], MOI 0.33 [center], or other MOI [bottom]) was plotted in relation to the time (in days) from the date of vector manufacture. Simple linear regression was used to generate a trend for each cell product produced. Two lots were not included in the simple linear regression analysis due to limited manufacture of clinical products (minimum required is 3).