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.
Highlights
Viruses are infectious agents composed of nucleic acids protected by a protein coat.These microbes cannot self-replicate, relying instead on the cells they infect to produce more copies of themselves by hijacking the host’s replication machinery [1]
The transduction of a single leukaemia B cell led to the development of a resistant transgenic clone in a patient treated with the anti-CD19 Chimeric Antigen Receptor (CAR) T cell therapy tisagenlecleucel (Kymriah) [94]
T cell Receptor (TCR) T cell therapy is an alternative to CAR-transduced T cells for targeting malignancies
Summary
Viruses are infectious agents composed of nucleic acids protected by a protein coat. These microbes cannot self-replicate, relying instead on the cells they infect to produce more copies of themselves by hijacking the host’s replication machinery [1]. Viruses are generally associated with disease, but genetic engineers have repurposed their biology to leverage their natural ability to modify or supplement the host cell genetic code, producing a new class of gene delivery tools known as viral vectors [2]. The third and most recent generation of LV production system modified the 5 HIV LTR sequence of the transfer plasmid and replaced it with a strong viral promoter, such as the CMV or Rous sarcoma virus (RSV) promoters, allowing the removal of tat from the system and further preventing the formation of RCLs. the Rev element was removed from the packaging plasmid and loaded onto a new regulatory plasmid, resulting in a four-plasmid system for added safety against RCL formation [31].
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
