Immunogenicity of Lentiviral Vectors
Lentiviral vectors have been widely studied for use in gene therapy1
Two ex vivo gene therapies that use lentiviral vectors have received regulatory approval2,3
Immune responses to both the vector and transgene are still a concern1
Example: Tisagenlecleucel*: a lentiviral-vector delivered CAR T-cell therapy
- Treatment with tisagenlecleucel is associated with a risk of cytokine release syndrome2
- The presence of pre-existing or treatment-induced antibodies is not thought to
impact upon its safety and efficacy2
Lentiviral vectors can trigger an innate immune response1,4
Lentiviral-binding antibodies and activated complement components can opsonize (i.e. tag) lentiviral vectors1,5
This marks the lentiviral vectors for phagocytosis by liver and spleen macrophages and APCs1
Lentiviral vectors can trigger an adaptive immune response, which can be characterized as either humoral or cell-mediated1,4
Humoral Immunity
Lentiviral vectors are engineered with surface proteins from an unrelated virus – this is called pseudotyping1
Vesicular stomatitis virus (VSV) surface glycoprotein is commonly used to pseudotype lentiviral vectors1
Pre-existing antibodies against lentiviral vectors are less prevalent compared with other viral vectors as humans are not a natural host for VSV infection1
However, humans may carry non-specific cross-reacting anti-VSV.G antibodies1
Cell-Mediated Immunity
Lentiviral-derived viral antigens can induce a cell-mediated immune response and transgene-derived antigens can cause cytotoxic T cells to destroy transduced cells1
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- Annoni A, et al. Cell Immunol 2018; pii: S0008-8749(18)30187-4. doi: 10.1016/j.cellimm.2018.04.012;
- Kymriah® [package insert]. East Hanover, NJ; Novartis Pharmaceuticals Corporation; 2018. Available at: https://www.pharma.us.novartis.com/sites/www.pharma.us.novartis.com/files/kymriah.pdf. Accessed July 24, 2019;
- ZyntegloTM [summary of product characteristics]. Utrecht, The Netherlands; bluebird bio (Netherlands) B.V.; 2019. Available at: https://www.ema.europa.eu/en/documents/product-information/zynteglo-epar-product-information_en.pdf. Accessed July 24, 2019.
- Nayak S, Herzog RW. Gene Ther 2010;17(3):295–304;
- Thau L. Mahajan K. Physiology, Opsonization: StatPearls, December 2018. Available at: https://www.ncbi.nlm.nih.gov/books/NBK534215/. Accessed April 29, 2019.