001     302016
005     20250904143553.0
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041 _ _ |a English
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100 1 _ |a Poelchen, Juliane
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245 _ _ |a Generation and functional analysis of melanoma antigen-specific CD8+ T cells derived from S/MAR vector-transfected human induced pluripotent stem cells.
260 _ _ |a Bognor Regis
|c 2025
|b Wiley-Liss
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500 _ _ |a #EA:A370#LA:A370# / 2025 Nov 1;157(9):1876-1887
520 _ _ |a Melanoma accounts for the majority of all skin cancer-related deaths with rising incidence rates. Adoptive cell therapies (ACT) with tumor antigen-specific CD8+ T cells derived from human-induced pluripotent stem cells (hiPSCs) might offer a promising treatment strategy for advanced malignant melanoma patients. In this study, we investigated two strategies for the generation of CD8+ T cells from hiPSCs expressing a T cell receptor (TCR) specific for the melanoma-associated antigen recognized by T cells (MART-1) or a chimeric antigen receptor (CAR) specific for the melanoma-associated chondroitin sulfate proteoglycan (MCSP), respectively. While the long-term co-culture of bioengineered OP9 stromal cells with CD34+ hematopoietic stem/progenitor cells (HSPCs) facilitated the generation of CD4 + CD8+ double-positive (DP) T cells, we encountered difficulties in obtaining high percentages of CD8+ single-positive (SP) T cells using this method. However, the replacement of the OP9 cells with a T cell differentiation kit enabled the generation of CD8+ SP T cells after 47 days. Despite a low expression of the T cell marker CD3 on the surface of the generated CD8+ SP T cells, we detected intracellular IFN-γ and surface CD107a expression upon stimulation. Moreover, the generated CD8+ SP T cells exhibited cytotoxic effects when co-cultured with melanoma cell lines. The use of scaffold/matrix attachment region (S/MAR) DNA vectors ensured persistent expression of the TCR or the CAR during differentiation of T cells. Hence, these findings demonstrate the potential as well as the challenges associated with using S/MAR DNA vector-transfected hiPSCs for the generation of melanoma antigen-specific CD8+ T cells.
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650 _ 7 |a T cells
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650 _ 7 |a adoptive cell therapy
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650 _ 7 |a hiPSCs. S/MAR vector
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650 _ 7 |a melanoma
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700 1 _ |a Pardo, Sandra
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700 1 _ |a Novak, Daniel
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700 1 _ |a Sun, Qian
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700 1 _ |a Steinfass, Tamara
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700 1 _ |a Vierthaler, Marlene
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700 1 _ |a Cicek Sener, Özge
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700 1 _ |a Granados Blanco, Karol
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700 1 _ |a Wang, Yiman
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700 1 _ |a Nicolay, Jan Peter
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700 1 _ |a Guermonprez, Pierre
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700 1 _ |a Harbottle, Richard
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700 1 _ |a Umansky, Viktor
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700 1 _ |a Utikal, Jochen
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