TY  - JOUR
AU  - Seidmann, Larissa
AU  - Wingerter, Arthur
AU  - Oliver Metzig, Marie
AU  - Bornas, Angelina
AU  - El Malki, Khalifa
AU  - Ustjanzew, Arsenij
AU  - Ortmüller, Franziska
AU  - Kamyshanskiy, Yevgeniy
AU  - Kindler, Thomas
AU  - Laible, Mark
AU  - Mohr, Xenia
AU  - Henninger, Nicole
AU  - Russo, Alexandra
AU  - Beck, Olaf
AU  - Alt, Francesca
AU  - Wehling, Pia
AU  - Roth, Wilfried
AU  - Paret, Claudia
AU  - Faber, Jörg
TI  - The Chimeric Antigen Receptor T Cell Target Claudin 6 Is a Marker for Early Organ-Specific Epithelial Progenitors and Is Expressed in Some Pediatric Solid Tumor Entities.
JO  - Cancers
VL  - 17
IS  - 6
SN  - 2072-6694
CY  - Basel
PB  - MDPI
M1  - DKFZ-2025-00657
SP  - 920
PY  - 2025
AB  - Background/Objectives: The oncofetal membrane protein Claudin 6 (CLDN6) is an attractive target for T cell-based therapies. There is a lack of detailed analyses on the age-dependent expression of CLDN6 in normal tissues is lacking, which limits the expansion of CLDN6 CAR-T cell clinical trials to pediatric populations. Methods: We analyzed CLDN6 expression in extracranial solid tumors and normal tissues of children using RNA-sequencing data from over 500 pediatric solid tumor samples, qRT-PCR and immunohistochemistry (IHC) in more than 100 fresh-frozen tumor samples and, approximately, 250 formalin-fixed paraffin-embedded (FFPE) samples. We examined normal tissue expression via qRT-PCR in 32 different infant tissues and via IHC in roughly 290 tissues from donors across four age groups, as well as in fetal autopsy samples. Results: In fetal tissues, we detected CLDN6 expression primarily in the epithelial cells of several organs, including the skin, lungs, kidneys, intestinal tract, and pancreas, but not in undifferentiated blastemal cells. Postnatally, we found CLDN6-positive epithelial progenitors only during the first few weeks of life. In older-age groups, isolated clusters of CLDN6-positive progenitors were present, but in scarce quantities. In tumor tissues, we found strong and homogeneous CLDN6 expression in desmoplastic small round cell tumors and germ cell tumors. Wilms tumors demonstrated heterogeneous CLDN6 expression, notably absent in the blastemal component. Conclusions: These findings highlight an organ-specific presence of CLDN6-positive epithelial precursors that largely disappear in terminally differentiated epithelia within weeks after birth. Therefore, our data support CLDN6 as a viable therapeutic target in pediatric patients and justify their inclusion in basket studies for anti-CLDN6-based therapies.
KW  - CAR-T cells (Other)
KW  - Claudin 6 (Other)
KW  - Wilms tumors (Other)
KW  - desmoplastic small round cell tumors (Other)
KW  - germ cell tumors (Other)
LB  - PUB:(DE-HGF)16
C6  - pmid:40149257
C2  - pmc:PMC11940025
DO  - DOI:10.3390/cancers17060920
UR  - https://inrepo02.dkfz.de/record/300180
ER  -