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Nuclear reprogramming is a process of transforming one cell type into an unrelated cell type by epigenetic changes that alter the cell’s original gene expression pattern. Such epigenetic changes force cells to express a different set of genes, which play a significant role in inducing transformation into other cell types. Nuclear reprogramming offers applications in reproductive cloning for livestock propagation and regenerative medicine — developing patient-specific cells for...
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Author Spotlight: Advancements in CAR-T Cell Manufacturing and Gene Therapy Production
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Steering CAR T cell epigenetic programs by tweaking manufacturing protocol.

Meghan W Dukes1, Giedre Krenciute1

  • 1Department of Bone Marrow Transplantation and Cellular Therapy, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.

Cell Reports. Medicine
|June 21, 2023
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Summary

Enhancing CAR T-cell persistence is crucial for treating solid and brain tumors. Simple manufacturing modifications can enrich resident memory phenotypes, improving CAR T-cell effectiveness.

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Area of Science:

  • Immunotherapy
  • Cellular Therapy
  • Oncology

Background:

  • CAR T-cell therapy shows promise but faces challenges in clinical translation, particularly for solid and brain tumors.
  • Limited persistence of CAR T-cells is a significant roadblock to their effective use in treating these challenging cancers.

Purpose of the Study:

  • To investigate methods for improving CAR T-cell persistence.
  • To explore simple modifications in the CAR T-cell manufacturing process to enhance therapeutic efficacy.

Main Methods:

  • The study focused on altering the CAR T-cell manufacturing process.
  • Specific changes were implemented to enrich for particular T-cell phenotypes.

Main Results:

  • The researchers successfully enriched resident memory phenotypes within the CAR T-cell population.
  • These modifications led to improved CAR T-cell persistence, a key factor for sustained anti-tumor activity.

Conclusions:

  • Simple adjustments to CAR T-cell manufacturing can significantly enhance the persistence of resident memory phenotypes.
  • This approach offers a promising strategy to overcome a major hurdle in the clinical application of CAR T-cells for solid and brain tumors.