Challenges of translating a cell therapy to GMP.

ABSTRACT

Over the last decade, cell and gene therapies have contributed remarkably to the array of novel therapies combating diseases that did not have any hope for an effective treatment or, let alone, a cure. This remarkable achievement was underlined by the marketing approval of CAR T cell therapies in 2017 in the United States, followed by many other countries, world-wide. Since then, thousands of patients have benefited from this autologous, gene modified cell therapy (Abou-El-Enein et al., 2021). Rare diseases, particularly innate neurological diseases such as Huntington's disease have also been a target for cell therapies. The notion of being able to augment or replace the function of diseased neurons with progenitor cells or neurons derived from human stem cells has been researched for the last 10 years and is finally reaching the stage of clinical translation (Holley et al., 2018; Reidling et al., 2018). With these cellular and gene therapies reaching clinical applicability, it is important to bring them to patients in a safe, efficacious and reliable way, and for this purpose, Good Manufacturing Practice (GMP) needs to be applied to the manufacturing of such novel and often life-saving therapies. In the first decade of the 21st century, gene therapies, particularly in vivo adenoviral vector gene therapy (Wilson, 2009) and hematopoietic stem cell gene therapies (Hacein-Bey-Abina et al., 2008) were associated with adverse events that were highly publicized and gave the field a bad reputation in the public eye. The last two decades, however, due to the meticulous work of dedicated researchers, and excellent progress in GMP manufacturing, cell and gene therapies have become safe and efficacious and have propelled the field to the forefront of the most promising novel therapies available for current unmet medical needs. This book chapter will discuss the historical perspective of cellular therapies and their development, will describe the currently available cell and gene therapies for different diseases and their GMP manufacturing methods and challenges, and will point out the future direction of these therapies and their envisioned manufacturing, as can be foreseen currently.