Reprogramming of Melanoma Tumor-Infiltrating Lymphocytes to Induced Pluripotent Stem Cells
Induced pluripotent stem cells (iPSCs) derived from somatic cells of patients hold great promise for autologous cell therapies. One of the possible applications of iPSCs is to use them as a cell source for producing autologous lymphocytes for cell-based therapy against cancer. Tumor-infiltrating lym...
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| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2016-01-01
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| Series: | Stem Cells International |
| Online Access: | http://dx.doi.org/10.1155/2016/8394960 |
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| _version_ | 1832552433542234112 |
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| author | Hidehito Saito Keisuke Okita Noemi Fusaki Michael S. Sabel Alfred E. Chang Fumito Ito |
| author_facet | Hidehito Saito Keisuke Okita Noemi Fusaki Michael S. Sabel Alfred E. Chang Fumito Ito |
| author_sort | Hidehito Saito |
| collection | DOAJ |
| description | Induced pluripotent stem cells (iPSCs) derived from somatic cells of patients hold great promise for autologous cell therapies. One of the possible applications of iPSCs is to use them as a cell source for producing autologous lymphocytes for cell-based therapy against cancer. Tumor-infiltrating lymphocytes (TILs) that express programmed cell death protein-1 (PD-1) are tumor-reactive T cells, and adoptive cell therapy with autologous TILs has been found to achieve durable complete response in selected patients with metastatic melanoma. Here, we describe the derivation of human iPSCs from melanoma TILs expressing high level of PD-1 by Sendai virus-mediated transduction of the four transcription factors, OCT3/4, SOX2, KLF4, and c-MYC. TIL-derived iPSCs display embryonic stem cell-like morphology, have normal karyotype, express stem cell-specific surface antigens and pluripotency-associated transcription factors, and have the capacity to differentiate in vitro and in vivo. A wide variety of T cell receptor gene rearrangement patterns in TIL-derived iPSCs confirmed the heterogeneity of T cells infiltrating melanomas. The ability to reprogram TILs containing patient-specific tumor-reactive repertoire might allow the generation of patient- and tumor-specific polyclonal T cells for cancer immunotherapy. |
| format | Article |
| id | doaj-art-599389fc6a59441b87fd9fbfc745581f |
| institution | Kabale University |
| issn | 1687-966X 1687-9678 |
| language | English |
| publishDate | 2016-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Stem Cells International |
| spelling | doaj-art-599389fc6a59441b87fd9fbfc745581f2025-02-03T05:58:36ZengWileyStem Cells International1687-966X1687-96782016-01-01201610.1155/2016/83949608394960Reprogramming of Melanoma Tumor-Infiltrating Lymphocytes to Induced Pluripotent Stem CellsHidehito Saito0Keisuke Okita1Noemi Fusaki2Michael S. Sabel3Alfred E. Chang4Fumito Ito5Department of Surgery, University of Michigan, 1500 E Medical Center Drive, 3410 CC, Ann Arbor, MI 48109-5932, USACenter for iPS Cell Research and Application, Kyoto, JapanDepartment of Ophthalmology, Keio University School of Medicine, Tokyo, JapanDepartment of Surgery, University of Michigan, 1500 E Medical Center Drive, 3410 CC, Ann Arbor, MI 48109-5932, USADepartment of Surgery, University of Michigan, 1500 E Medical Center Drive, 3410 CC, Ann Arbor, MI 48109-5932, USADepartment of Surgery, University of Michigan, 1500 E Medical Center Drive, 3410 CC, Ann Arbor, MI 48109-5932, USAInduced pluripotent stem cells (iPSCs) derived from somatic cells of patients hold great promise for autologous cell therapies. One of the possible applications of iPSCs is to use them as a cell source for producing autologous lymphocytes for cell-based therapy against cancer. Tumor-infiltrating lymphocytes (TILs) that express programmed cell death protein-1 (PD-1) are tumor-reactive T cells, and adoptive cell therapy with autologous TILs has been found to achieve durable complete response in selected patients with metastatic melanoma. Here, we describe the derivation of human iPSCs from melanoma TILs expressing high level of PD-1 by Sendai virus-mediated transduction of the four transcription factors, OCT3/4, SOX2, KLF4, and c-MYC. TIL-derived iPSCs display embryonic stem cell-like morphology, have normal karyotype, express stem cell-specific surface antigens and pluripotency-associated transcription factors, and have the capacity to differentiate in vitro and in vivo. A wide variety of T cell receptor gene rearrangement patterns in TIL-derived iPSCs confirmed the heterogeneity of T cells infiltrating melanomas. The ability to reprogram TILs containing patient-specific tumor-reactive repertoire might allow the generation of patient- and tumor-specific polyclonal T cells for cancer immunotherapy.http://dx.doi.org/10.1155/2016/8394960 |
| spellingShingle | Hidehito Saito Keisuke Okita Noemi Fusaki Michael S. Sabel Alfred E. Chang Fumito Ito Reprogramming of Melanoma Tumor-Infiltrating Lymphocytes to Induced Pluripotent Stem Cells Stem Cells International |
| title | Reprogramming of Melanoma Tumor-Infiltrating Lymphocytes to Induced Pluripotent Stem Cells |
| title_full | Reprogramming of Melanoma Tumor-Infiltrating Lymphocytes to Induced Pluripotent Stem Cells |
| title_fullStr | Reprogramming of Melanoma Tumor-Infiltrating Lymphocytes to Induced Pluripotent Stem Cells |
| title_full_unstemmed | Reprogramming of Melanoma Tumor-Infiltrating Lymphocytes to Induced Pluripotent Stem Cells |
| title_short | Reprogramming of Melanoma Tumor-Infiltrating Lymphocytes to Induced Pluripotent Stem Cells |
| title_sort | reprogramming of melanoma tumor infiltrating lymphocytes to induced pluripotent stem cells |
| url | http://dx.doi.org/10.1155/2016/8394960 |
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