Abstract:
:Adoptive cell transfer (ACT) of antigen (Ag)-specific CD8(+) cytotoxic T lymphocytes (CTLs) is a highly promising treatment for a variety of diseases. Naive or central memory T-cell-derived effector CTLs are optimal populations for ACT-based immunotherapy because these cells have a high proliferative potential, are less prone to apoptosis than terminally differentiated cells, and have the higher ability to respond to homeostatic cytokines. However, such ACT with T-cell persistence is often not feasible due to difficulties in obtaining sufficient cells from patients. Here we present that in vitro differentiated HSCs of engineered PSCs can develop in vivo into tumor Ag-specific naive CTLs, which efficiently suppress melanoma growth. Mouse-induced PSCs (iPSCs) were retrovirally transduced with a construct encoding chicken ovalbumin (OVA)-specific T-cell receptors (TCRs) and survival-related proteins (i.e., BCL-xL and survivin). The gene-transduced iPSCs were cultured on the delta-like ligand 1-expressing OP9 (OP9-DL1) murine stromal cells in the presence of murine recombinant cytokines (rFlt3L and rIL-7) for a week. These iPSC-derived cells were then intravenously adoptively transferred into recipient mice, followed by intraperitoneal injection with an agonist α-Notch 2 antibody and cytokines (rFlt3L and rIL-7). Two weeks later, naive OVA-specific CD8(+) T cells were observed in the mouse peripheral lymphatic system, which were responsive to OVA-specific stimulation. Moreover, the mice were resistant to the challenge of B16-OVA melanoma induction. These results indicate that genetically modified stem cells may be used for ACT-based immunotherapy or serve as potential vaccines.
journal_name
Cell Transplantjournal_title
Cell transplantationauthors
Haque M,Song J,Fino K,Sandhu P,Wang Y,Ni B,Fang D,Song Jdoi
10.3727/096368916X690467subject
Has Abstractpub_date
2016-01-01 00:00:00pages
811-27issue
5eissn
0963-6897issn
1555-3892pii
content-CT-2562_Haque_et_aljournal_volume
25pub_type
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journal_title:Cell transplantation
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journal_title:Cell transplantation
pub_type: 杂志文章,评审
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doi:10.3727/096368909788809839
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更新日期:2017-04-13 00:00:00
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journal_title:Cell transplantation
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doi:10.1016/s0963-6897(97)00099-7
更新日期:1997-11-01 00:00:00
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更新日期:2011-01-01 00:00:00
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