Notch Signaling Switch Enables Scalable Helper T Cell Production for CAR T
By modulating Notch and T cell receptor signaling, scientists have produced functional CD4+ T cells from iPSCs, potentially advancing scalable, off-the-shelf CAR T therapies. The post Notch Signaling Switch Enables Scalable Helper T Cell Production for CAR T appeared first on GEN - Genetic Engineering and Biotechnology News .
A new study published in Stem Cell Reports details a method developed by researchers at Boston University’s Center for Regenerative Medicine and Boston Medical Center to generate CD4+ helper T cells from induced pluripotent stem cells (iPSCs) on a scalable basis. This approach could facilitate the production of off-the-shelf CAR T-cell therapies for patients with various cancers and chronic inflammatory diseases.
The study, led by Gustavo Mostoslavsky, MD, PhD, and Julian Amirault, a doctoral student, focuses on the Notch molecular signaling pathway, which plays a crucial role in early T cell development. The researchers discovered that by removing Notch signaling during the later stages of T cell maturation while simultaneously reducing anti-T cell receptor signaling, they could successfully produce large quantities of functional CD4+ T cells.
Notch signaling is essential for the initial development of T cells, but this study shows that modulating it can help these cells mature into functional helper CD4+ T cells. This approach results in T cells that closely resemble those found in human blood, possessing a complete array of different subtypes. In addition to its potential clinical applications, the study provides valuable insights into T-cell biology, particularly regarding the dynamic nature of Notch signaling during T cell development and its influence on the differentiation of cells into either CD8 or CD4 lineages.
The next step for the researchers involves introducing chimeric antigen receptors directly into the iPSC-derived CD4+ and CD8+ cells and evaluating their ability to target and eliminate cancer cells in animal models. Mostoslavsky envisions a future where these cells could be readily available when a patient is diagnosed, eliminating the need for cell collection and individualized manufacturing processes, ultimately streamlining the treatment of various diseases.
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