Journal Article

DKFZ-2025-01214

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Generation and functional analysis of melanoma antigen-specific CD8+ T cells derived from S/MAR vector-transfected human induced pluripotent stem cells.

Poelchen, J. (First author)DKFZ* ; Pardo, S.DKFZ* ; Novak, D.DKFZ* ; Sun, Q.DKFZ* ; Steinfass, T.DKFZ* ; Vierthaler, M.DKFZ* ; Cicek Sener, Ö.DKFZ* ; Granados Blanco, K.DKFZ* ; Wang, Y.DKFZ* ; Nicolay, J. P.DKFZ* ; Guermonprez, P. ; Harbottle, R.DKFZ* ; Umansky, V.DKFZ* ; Utikal, J. (Last author)DKFZ*

2025
Wiley-Liss Bognor Regis

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Please use a persistent id in citations: doi:10.1002/ijc.35524

Abstract: 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.

Keyword(s): T cells ; adoptive cell therapy ; hiPSCs. S/MAR vector ; melanoma

Note: #EA:A370#LA:A370# / 2025 Nov 1;157(9):1876-1887

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Contributing Institute(s):

1. KKE Dermatoonkologie (A370)
2. DNA-Vektoren (D420)

Research Program(s):

1. 311 - Zellbiologie und Tumorbiologie (POF4-311) (POF4-311)

Appears in the scientific report 2025

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Database coverage:
; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Life Sciences ; DEAL Wiley ; Essential Science Indicators ; IF >= 5 ; JCR ; Nationallizenz ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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