A Serum- and Feeder-Free System to Generate CD4 and Regulatory T Cells from Human iPSCs

Fong, Helen; Mendel, Matthew; Jascur, John; Najmi, Laeya; Kim, Ken; Lew, Garrett; Garimalla, Swetha; Schock, Suruchi; Hu, Jing; Villegas, Andres; Conway, Anthony; Fontenot, Jason D.; Zompi, Simona

doi:10.1101/2023.07.01.547333

Cited by 2 publications

References 79 publications

(148 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

Matching or genetic engineering of HLA Class I and II facilitates successful allogeneic ‘off-the-shelf’ regulatory T cell therapy

McCallion,

Du,

Glaser

et al. 2023

Preprint

View full text Add to dashboard Cite

The potential to harness regulatory T cells (Tregs) for the treatment of autoimmune diseases and transplant rejection has been restricted by several barriers: donor variability, manufacturing complications, and time-consuming expansion processes. These issues further complicate the use of autologous Tregs during acute disease phases or when Tregs are low in number or dysfunctional. Here we explore the potential of 'off-the-shelf' allogeneic Tregs, from healthy donors or universal sources, to provide a more practical solution. We discover that the efficacy of these cells is undermined by the recipient's immune response, and that that rigorous matching of HLA classes I and II overcomes this barrier. Importantly, genetically manipulating HLA expression enables the use of unmatched allogeneic Tregs with in vivo efficacy. Our findings underscore the transformative potential of HLA-engineered Tregs, offering a novel, ready-to-use therapeutic avenue for treating a wide array of inflammatory diseases.

show abstract

Matching or genetic engineering of HLA Class I and II facilitates successful allogeneic ‘off-the-shelf’ regulatory T cell therapy

McCallion,

Du,

Glaser

et al. 2023

Preprint

View full text Add to dashboard Cite

show abstract

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

Netsrithong,

Garcia-Perez,

Themeli

2024

Front. Immunol.

View full text Add to dashboard Cite

Induced pluripotent stem cell (iPSC)-derived T (iT) cells represent a groundbreaking frontier in adoptive cell therapies with engineered T cells, poised to overcome pivotal limitations associated with conventional manufacturing methods. iPSCs offer an off-the-shelf source of therapeutic T cells with the potential for infinite expansion and straightforward genetic manipulation to ensure hypo-immunogenicity and introduce specific therapeutic functions, such as antigen specificity through a chimeric antigen receptor (CAR). Importantly, genetic engineering of iPSC offers the benefit of generating fully modified clonal lines that are amenable to rigorous safety assessments. Critical to harnessing the potential of iT cells is the development of a robust and clinically compatible production process. Current protocols for genetic engineering as well as differentiation protocols designed to mirror human hematopoiesis and T cell development, vary in efficiency and often contain non-compliant components, thereby rendering them unsuitable for clinical implementation. This comprehensive review centers on the remarkable progress made over the last decade in generating functional engineered T cells from iPSCs. Emphasis is placed on alignment with good manufacturing practice (GMP) standards, scalability, safety measures and quality controls, which constitute the fundamental prerequisites for clinical application. In conclusion, the focus on iPSC as a source promises standardized, scalable, clinically relevant, and potentially safer production of engineered T cells. This groundbreaking approach holds the potential to extend hope to a broader spectrum of patients and diseases, leading in a new era in adoptive T cell therapy.

show abstract

A Serum- and Feeder-Free System to Generate CD4 and Regulatory T Cells from Human iPSCs

Cited by 2 publications

References 79 publications

Matching or genetic engineering of HLA Class I and II facilitates successful allogeneic ‘off-the-shelf’ regulatory T cell therapy

Matching or genetic engineering of HLA Class I and II facilitates successful allogeneic ‘off-the-shelf’ regulatory T cell therapy

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

Contact Info

Product

Resources

About