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@ARTICLE{Poelchen:302016,
author = {J. Poelchen$^*$ and S. Pardo$^*$ and D. Novak$^*$ and Q.
Sun$^*$ and T. Steinfass$^*$ and M. Vierthaler$^*$ and Ö.
Cicek Sener$^*$ and K. Granados Blanco$^*$ and Y. Wang$^*$
and J. P. Nicolay$^*$ and P. Guermonprez and R.
Harbottle$^*$ and V. Umansky$^*$ and J. Utikal$^*$},
title = {{G}eneration and functional analysis of melanoma
antigen-specific {CD}8+ {T} cells derived from {S}/{MAR}
vector-transfected human induced pluripotent stem cells.},
journal = {International journal of cancer},
volume = {157},
number = {9},
issn = {0020-7136},
address = {Bognor Regis},
publisher = {Wiley-Liss},
reportid = {DKFZ-2025-01214},
pages = {1876-1887},
year = {2025},
note = {#EA:A370#LA:A370# / 2025 Nov 1;157(9):1876-1887},
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.},
keywords = {T cells (Other) / adoptive cell therapy (Other) / hiPSCs.
S/MAR vector (Other) / melanoma (Other)},
cin = {A370 / D420},
ddc = {610},
cid = {I:(DE-He78)A370-20160331 / I:(DE-He78)D420-20160331},
pnm = {311 - Zellbiologie und Tumorbiologie (POF4-311)},
pid = {G:(DE-HGF)POF4-311},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:40504044},
doi = {10.1002/ijc.35524},
url = {https://inrepo02.dkfz.de/record/302016},
}