The study examined secukinumab biosimilar lentivirus-based gene therapy, which showed successful and prolonged expression of the recombinant antibody in rats.
Researchers say biosimilar gene therapy could become a cost-effective, long-term treatment for autoimmune diseases, according to a recent study; their work looked at secukinumab biosimilar lentivirus-based gene therapy, which showed successful and prolonged expression of the recombinant antibody in rats.
Producing, transporting, storing, and administering monoclonal antibodies is time-consuming and costly. According to the researchers, if patients’ own cells could be used to manufacture a biosimilar, manufacturing, transportation, and storage steps could be eliminated, while providing a longer-lasting source of the drug potentially at a lower cost.
Secukinumab (Cosentyx) binds to IL-17A, inhibiting its interaction with the IL-17 receptor; secukinumab is prescribed for plaque psoriasis, psoriatic arthritis, and ankylosing spondylitis. The universality of IL-17’s involvement in autoimmune diseases made this particular drug attractive to the researchers.
Biosimilar gene therapy was tested in both ex vivo and in vivo experiments. Human chorionic villous mesenchymal stem cells (CMSCs) were isolated and transduced with a lentiviral vector containing the DNA sequences of the heavy and light chains of secukinumab, which were derived from the secukinumab protein sequence. In one group of rats, the transduced CMSCs were injected. In another group, the lentivirus was injected, and the rats were monitored for 60 days.
Expression of recombinant secukinumab at the mRNA and protein levels was confirmed in the transduced CMSCs, and the secreted antibody’s ability to inhibit IL-17 was confirmed in human fibroblasts. In both transduced CMSC and lentivirus injected rats, the presence of secukinumab in the bloodstream was confirmed at various points throughout the 60 day period.
The serum concentration of the antibody was higher in lentivirus treated rats compared to CMSC treated rats. However, the authors noted these concentrations were substantially lower than those currently approved for administration of secukinumab, and that improved serum concentrations would be necessary for human application of this therapy.
Fallah A, Estiri H, Parrish E, Soleimani M, Zeinali S, Zadeh-Vakili A. Biosimilar gene therapy: Investigational assessment of secukinumab gene therapy. Cell J. 2020;21(4):433—443. doi:10.22074/cellj.2020.6309