Engineered T cells from induced pluripotent stem cells: from research towards clinical implementation

Engineered T cells from induced pluripotent stem cells: from research towards clinical implementation

12 January 2024 | Ratchapong Netsrithong, Laura Garcia-Perez and Maria Themeli
The article "Engineered T cells from induced pluripotent stem cells: from research towards clinical implementation" by Ratchapong Netsirihong, Laura Garcia-Perez, and Maria Themeli reviews the progress in generating functional engineered T cells (iT cells) and chimeric antigen receptor (CAR) T cells (iCAR T cells) from induced pluripotent stem cells (iPSCs). The authors highlight the advantages of iPSC-derived T cells, including infinite expansion, straightforward genetic manipulation, and the potential for hypo-immunogenicity and specific therapeutic functions. However, the current protocols for genetic engineering and differentiation often lack clinical compatibility due to non-compliant components and variability in efficiency. The review emphasizes the importance of aligning with good manufacturing practice (GMP) standards, scalability, safety measures, and quality controls for clinical application. Key aspects discussed include the reprogramming process, donor cell of origin, universally applicable iPSC clones, expression of CAR transgenes, gene editing, and safeguard systems. The authors also detail the challenges and advancements in cGMP-generation of engineered iPSC clones, including donor acquisition, reprogramming methods, culture media, and quality control testing. In the context of differentiating iPSCs towards hematopoietic cells, the article covers the physiological developmental processes, methods for generating hematopoietic stem and progenitor cells (HSPCs), and in vitro T lymphoid development. It discusses the use of murine stromal cells, embryoid bodies, and monolayer systems, as well as feeder-free and serum-free approaches. The article concludes by highlighting the potential of iPSC-derived T cells for standardized, scalable, and clinically relevant production, offering hope for broader applications in cancer, infectious diseases, autoimmune diseases, and transplantation.The article "Engineered T cells from induced pluripotent stem cells: from research towards clinical implementation" by Ratchapong Netsirihong, Laura Garcia-Perez, and Maria Themeli reviews the progress in generating functional engineered T cells (iT cells) and chimeric antigen receptor (CAR) T cells (iCAR T cells) from induced pluripotent stem cells (iPSCs). The authors highlight the advantages of iPSC-derived T cells, including infinite expansion, straightforward genetic manipulation, and the potential for hypo-immunogenicity and specific therapeutic functions. However, the current protocols for genetic engineering and differentiation often lack clinical compatibility due to non-compliant components and variability in efficiency. The review emphasizes the importance of aligning with good manufacturing practice (GMP) standards, scalability, safety measures, and quality controls for clinical application. Key aspects discussed include the reprogramming process, donor cell of origin, universally applicable iPSC clones, expression of CAR transgenes, gene editing, and safeguard systems. The authors also detail the challenges and advancements in cGMP-generation of engineered iPSC clones, including donor acquisition, reprogramming methods, culture media, and quality control testing. In the context of differentiating iPSCs towards hematopoietic cells, the article covers the physiological developmental processes, methods for generating hematopoietic stem and progenitor cells (HSPCs), and in vitro T lymphoid development. It discusses the use of murine stromal cells, embryoid bodies, and monolayer systems, as well as feeder-free and serum-free approaches. The article concludes by highlighting the potential of iPSC-derived T cells for standardized, scalable, and clinically relevant production, offering hope for broader applications in cancer, infectious diseases, autoimmune diseases, and transplantation.
Reach us at info@study.space
Understanding Engineered T cells from induced pluripotent stem cells%3A from research towards clinical implementation