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Related Concept Videos

iPS Cell Differentiation01:22

iPS Cell Differentiation

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The ability of induced pluripotent stem cells or iPSCs to differentiate into most body cell types has stimulated repair and regenerative medicine research over the past few decades. iPSC-derived blood cells, hepatocytes, beta islet cells, cardiomyocytes, neurons, and other cell types can repair injuries or regenerate damaged tissue in diseases such as diabetes and neurodegenerative disorders.
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Tumor Immunotherapy01:27

Tumor Immunotherapy

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Immunotherapy is a treatment that boosts or manipulates the immune system to fight diseases, including cancer. For instance, by stimulating an immune response through vaccinations against viruses that cause cancers, like hepatitis B virus and human papillomavirus, these diseases can be prevented. Nonetheless, some cancer cells can avoid the immune system due to their rapid mutation and division. The immune response to many cancers involves three phases: elimination, equilibrium, and escape.
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EPS and iPS Cells in Disease Research01:21

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Embryonic and induced pluripotent stem cells are excellent models for disease research because of their ability to self-renew and differentiate into most cell types. Somatic cells from a patient are isolated and reprogrammed into induced pluripotent stem cells or iPSCs. These iPSCs are later differentiated into the desired cell type, which mirrors the diseased cell of the patient. In this way, disease models have been created for investigating diseases such as Down syndrome, type I diabetes,...
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Induced Pluripotent Stem Cells01:06

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Stem cells are undifferentiated cells that divide and produce different cell types. Ordinarily, cells that have differentiated into a specific cell type are terminally differentiated; however, scientists have found a way to reprogram these mature cells so that they dedifferentiate and return to an unspecialized, proliferative state. These cells are pluripotent like embryonic stem cells—able to produce all cell types—and are called induced pluripotent stem cells (iPSCs).
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Related Experiment Video

Updated: Sep 12, 2025

Generation of Induced Pluripotent Stem Cells from Human Melanoma Tumor-infiltrating Lymphocytes
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[iPSC-derived next-generation T cell therapy for refractory malignancies].

Miki Ando1

  • 1Department of Hematology, Juntendo University School of Medicine.

[Rinsho Ketsueki] the Japanese Journal of Clinical Hematology
|August 6, 2025
PubMed
Summary

Researchers developed rejuvenated T cells from induced pluripotent stem cells (iPSCs) for enhanced cancer immunotherapy. These engineered cells exhibit potent tumor-killing activity and persistence, offering a promising "off-the-shelf" therapy.

Keywords:
CRISPR/Cas9 genome editingEB virus-associated lymphomaNext-generation T cell therapyiPSC-derived CTL

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Directed Differentiation of Induced Pluripotent Stem Cells towards T Lymphocytes
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Directed Differentiation of Induced Pluripotent Stem Cells towards T Lymphocytes

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Area of Science:

  • Immunology
  • Stem Cell Biology
  • Cancer Therapy

Context:

  • Cytotoxic T lymphocytes (CTLs) are crucial for tumor immunity but face limitations like senescence and antigen escape.
  • Induced pluripotent stem cells (iPSCs) offer a renewable source for cell therapy, but their differentiation into functional CTLs requires optimization.
  • Existing T cell therapies often struggle with limited persistence and patient-specific manufacturing.

Purpose:

  • To develop rejuvenated CTLs (rejTs) from iPSCs with enhanced anti-tumor activity and persistence.
  • To engineer rejTs with dual-antigen specificity (CAR and endogenous TCR) to overcome tumor antigen escape.
  • To create HLA class I-edited rejTs for reduced immunogenicity and improved allogeneic compatibility.

Summary:

  • Antigen-specific CTLs were reprogrammed into iPSCs and redifferentiated into rejuvenated CTLs (rejTs) with a youthful phenotype and potent tumor-killing capacity.
  • Chimeric antigen receptor (CAR) technology was introduced into rejTs for dual targeting of CD19 and EBV-LMP2 antigens, enhancing efficacy against EBV-associated lymphomas.
  • CRISPR/Cas9 was used to edit HLA class I on rejTs, minimizing immune rejection and improving cytotoxicity against virus-associated tumors, paving the way for allogeneic cell therapy.

Impact:

  • These next-generation rejTs demonstrate synergistic anti-tumor effects and prolonged in vivo persistence.
  • HLA-edited rejTs show reduced recipient immune rejection while maintaining robust anti-tumor cytotoxicity.
  • The developed rejTs represent a sustainable and scalable
  • off-the-shelf
  • T cell therapy approach.