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000302016 1001_ $$0P:(DE-He78)88a268b9173c651561385cddfdf819fa$$aPoelchen, Juliane$$b0$$eFirst author
000302016 245__ $$aGeneration and functional analysis of melanoma antigen-specific CD8+ T cells derived from S/MAR vector-transfected human induced pluripotent stem cells.
000302016 260__ $$aBognor Regis$$bWiley-Liss$$c2025
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000302016 500__ $$a#EA:A370#LA:A370# / 2025 Nov 1;157(9):1876-1887
000302016 520__ $$aMelanoma 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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000302016 650_7 $$2Other$$aT cells
000302016 650_7 $$2Other$$aadoptive cell therapy
000302016 650_7 $$2Other$$ahiPSCs. S/MAR vector
000302016 650_7 $$2Other$$amelanoma
000302016 7001_ $$0P:(DE-HGF)0$$aPardo, Sandra$$b1
000302016 7001_ $$0P:(DE-He78)5f0b1c9863f44d0695555ee3c22b9758$$aNovak, Daniel$$b2$$udkfz
000302016 7001_ $$0P:(DE-He78)f1f0076fc72606659a5df2605acce91b$$aSun, Qian$$b3$$udkfz
000302016 7001_ $$0P:(DE-He78)a65fa5fbdeff5a1bb6ee7de07b820488$$aSteinfass, Tamara$$b4
000302016 7001_ $$0P:(DE-He78)61de47f47323d5d0b1700e8213e5179f$$aVierthaler, Marlene$$b5
000302016 7001_ $$0P:(DE-HGF)0$$aCicek Sener, Özge$$b6
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000302016 7001_ $$0P:(DE-He78)ada7e359a1f7451130dbc79595227bec$$aWang, Yiman$$b8
000302016 7001_ $$0P:(DE-He78)7b847bc226706f4fc5a573f1483c49d9$$aNicolay, Jan Peter$$b9$$udkfz
000302016 7001_ $$aGuermonprez, Pierre$$b10
000302016 7001_ $$0P:(DE-He78)15dff5647002b4dcfe892b251cd14b62$$aHarbottle, Richard$$b11$$udkfz
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000302016 7001_ $$0P:(DE-He78)a229f7724466e7efadf4a1ace1ff8af3$$aUtikal, Jochen$$b13$$eLast author$$udkfz
000302016 773__ $$0PERI:(DE-600)1474822-8$$a10.1002/ijc.35524$$gp. ijc.35524$$n9$$p1876-1887$$tInternational journal of cancer$$v157$$x0020-7136$$y2025
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