%0 Journal Article
%A Poelchen, Juliane
%A Pardo, Sandra
%A Novak, Daniel
%A Sun, Qian
%A Steinfass, Tamara
%A Vierthaler, Marlene
%A Cicek Sener, Özge
%A Granados Blanco, Karol
%A Wang, Yiman
%A Nicolay, Jan Peter
%A Guermonprez, Pierre
%A Harbottle, Richard
%A Umansky, Viktor
%A Utikal, Jochen
%T Generation and functional analysis of melanoma antigen-specific CD8+ T cells derived from S/MAR vector-transfected human induced pluripotent stem cells.
%J International journal of cancer
%V 157
%N 9
%@ 0020-7136
%C Bognor Regis
%I Wiley-Liss
%M DKFZ-2025-01214
%P 1876-1887
%D 2025
%Z #EA:A370#LA:A370# / 2025 Nov 1;157(9):1876-1887
%X 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.
%K T cells (Other)
%K adoptive cell therapy (Other)
%K hiPSCs. S/MAR vector (Other)
%K melanoma (Other)
%F PUB:(DE-HGF)16
%9 Journal Article
%$ pmid:40504044
%R 10.1002/ijc.35524
%U https://inrepo02.dkfz.de/record/302016