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

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.

The interferon-induced protein kinase R: the base of a riboprotein scaffolding regulating the human immunodeficiency virus.

The interferon-induced RNA-activated Protein Kinase (PKR) targets the alpha subunit of the eukaryotic translation initiation factor 2 (eIF2α) whose phosphorylation blocks translation initiation of cellular and viral mRNAs. PKR is activated at the beginning of human immunodeficiency virus (HIV) infection by low levels of the HIV Transactivation Response (TAR) RNA and by the cellular PKR Activator (PACT), which contributes to a reduced viral replication. During HIV replication, the viral Tat protein and high production of TAR RNA decrease PKR activation.

The interferon-induced protein kinase R: the base of a riboprotein scaffolding regulating the human immunodeficiency virus.

The interferon-induced RNA-activated Protein Kinase (PKR) targets the alpha subunit of the eukaryotic translation initiation factor 2 (eIF2α) whose phosphorylation blocks translation initiation of cellular and viral mRNAs. PKR is activated at the beginning of human immunodeficiency virus (HIV) infection by low levels of the HIV Transactivation Response (TAR) RNA and by the cellular PKR Activator (PACT), which contributes to a reduced viral replication. During HIV replication, the viral Tat protein and high production of TAR RNA decrease PKR activation.