Lentiviral vectors for t cell engineering: Clinical applications, bioprocessing and future perspectives

Abstract

Lentiviral vectors have played a critical role in the emergence of gene-modified cell ther-apies, 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 rep-resent 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.