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Related Concept Videos

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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Related Experiment Video

Updated: Oct 24, 2025

Generation of Induced Pluripotent Stem Cells from Human Melanoma Tumor-infiltrating Lymphocytes
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iPSC-Derived Neoantigen-Specific CTL Therapy for Ewing Sarcoma.

Midori Ishii1,2, Jun Ando1,3, Satoshi Yamazaki4,5

  • 1Department of Hematology, Juntendo University School of Medicine, Bunkyo-ku, Tokyo, Japan.

Cancer Immunology Research
|August 13, 2021
PubMed
Summary
This summary is machine-generated.

Induced pluripotent stem cell-derived rejuvenated T-cells (rejTs) targeting the EWS/FLI1 neoantigen show potent antitumor effects against Ewing sarcoma. These rejTs offer a promising, less toxic alternative to conventional therapies for this aggressive cancer.

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Area of Science:

  • Immunology
  • Oncology
  • Stem Cell Biology

Background:

  • Ewing sarcoma prognosis is poor, particularly with metastasis, due to exhausted T-cells from continuous tumor antigen exposure.
  • Current therapies like chemotherapy and radiation have significant side effects, especially in adolescents.

Purpose of the Study:

  • To generate and evaluate the antitumor efficacy of induced pluripotent stem cell-derived functionally rejuvenated T-cells (rejTs) targeting the EWS/FLI1 neoantigen in Ewing sarcoma.

Main Methods:

  • Generated EWS/FLI1-specific rejTs from induced pluripotent stem cells derived from a healthy donor's T-cell clone.
  • Assessed rejT cytotoxicity against Ewing sarcoma cell lines in vitro.
  • Evaluated rejT antitumor effects and survival advantage in a Ewing sarcoma xenograft mouse model.

Main Results:

  • EWS/FLI1-rejTs demonstrated rapid and sustained suppression of Ewing sarcoma cell proliferation (>40 hours) in vitro.
  • In vivo studies confirmed significant antitumor effects and a statistically significant survival advantage in the xenograft mouse model.
  • Successful generation of EWS/FLI1-specific rejTs from iPSCs, despite low initial CTL frequency.

Conclusions:

  • EWS/FLI1-rejTs represent a novel therapeutic strategy targeting a specific Ewing sarcoma neoantigen.
  • This approach offers a potentially less destructive and disruptive treatment option compared to chemotherapy and radiation.
  • EWS/FLI1-rejTs hold promise as an "off-the-shelf" therapy for Ewing sarcoma, particularly for adolescent patients.