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Updated: Mar 27, 2026
10:03
Generation of Induced Pluripotent Stem Cells from Human Melanoma Tumor-infiltrating Lymphocytes
Published on: November 11, 2016
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Melanoma Immunotherapy in Mice Using Genetically Engineered Pluripotent Stem Cells.
Mohammad Haque1, Jianyong Song, Kristin Fino
1Department of Microbiology and Immunology, The Pennsylvania State University College of Medicine, Hershey, PA, USA.
Cell Transplantation
|January 19, 2016
Summary
Engineered stem cells can generate tumor-specific T cells for adoptive cell transfer (ACT) immunotherapy. These cells effectively suppressed melanoma growth in mice, offering potential for new cancer treatments and vaccines.
Area of Science:
- Immunology
- Stem Cell Biology
- Cancer Therapy
Background:
- Adoptive cell transfer (ACT) using antigen-specific CD8(+) cytotoxic T lymphocytes (CTLs) shows promise for disease treatment.
- Naive or central memory T-cell-derived CTLs are ideal for ACT due to their proliferative potential and resistance to apoptosis.
- Challenges exist in obtaining sufficient T cells for effective ACT.
Purpose of the Study:
- To investigate the potential of in vitro differentiated hematopoietic stem cells (HSCs) from engineered pluripotent stem cells (PSCs) to develop into tumor antigen-specific naive CTLs in vivo.
- To assess the efficacy of these engineered PSC-derived CTLs in suppressing melanoma growth.
Main Methods:
- Mouse-induced PSCs (iPSCs) were genetically modified to express chicken ovalbumin (OVA)-specific T-cell receptors (TCRs) and survival proteins (BCL-xL, survivin).
- Gene-transduced iPSCs were cultured on OP9-DL1 stromal cells with specific cytokines (rFlt3L, rIL-7).
- iPSC-derived cells were adoptively transferred into recipient mice, followed by treatment with an α-Notch 2 antibody and cytokines.
Main Results:
- Naive OVA-specific CD8(+) T cells were successfully generated in the peripheral lymphatic system of recipient mice.
- These T cells demonstrated responsiveness to OVA-specific stimulation.
- Mice treated with the engineered cells showed resistance to B16-OVA melanoma induction.
Conclusions:
- Genetically modified stem cells can differentiate into functional, tumor antigen-specific naive CTLs in vivo.
- This approach holds potential for developing novel strategies for ACT-based immunotherapy and cancer vaccines.
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