Journal Article

DKFZ-2026-01143

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png PSCA-directed nanosized bio-immune conjugates (NANO:BICs) enable selective uptake of TLR9 agonists in bladder cancer cells.

Iltzsche, M. ; Wetterling, N. ; Jilek, L. ; Nahhas, D. ; Hesse, M. ; Tietze, S. ; Temme, A.DKFZ* ; Thomas, C. ; Fuessel, S.DKFZ* ; Kind, B.

2026
Frontiers Media Lausanne

Abstract: Bladder cancer (BCa), particularly non-muscle invasive bladder cancer (NMIBC), remains a significant healthcare challenge due to high recurrence rates and limited non-surgical treatment options.Prostate stem cell antigen (PSCA)-transduced HEK-BlueTMhTLR9 and PSCA-positive SW780 bladder cancer cells were stimulated with PSCA-targeting NANO:BICs, which were assembled from a scFv(AM1)-KiBAP, NeutrAvidin, and the Toll-like Receptor 9 (TLR9) agonist ODN2006. Functional analyses included a secreted embryonic alkaline phosphatase (SEAP) reporter assay to measure TLR9 activation, a Cytometric Bead Array for cytokine quantification, and confocal microscopy to assess cellular uptake.PSCA-targeting NANO:BICs demonstrated significantly enhanced uptake into PSCA-positive cancer cells compared to non-targeting controls, with the PSCA receptor increasing uptake by a factor of 3.63. This targeted delivery led to potent activation of the TLR9 signaling pathway, evidenced by a robust reporter gene response and secretion of key antiviral cytokines, including type I and III interferons and the chemokine IP-10.These findings highlight the potential of this approach not only for reinvigorating anti-tumor immune responses in BCa but also for broader applications in other PSCA-expressing malignancies.

Keyword(s): NANO:BICs ; NMIBC ; PSCA ; bladder cancer ; fluorescence intensity analysis ; immunotherapy ; single-chain antibodies ; targeted therapy

Note: #DKTKZFB9# / #NCTZFB9#

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Contributing Institute(s):

1. DKTK Koordinierungsstelle Dresden (DD01)
2. Koordinierungsstelle NCT Dresden (DD04)

Research Program(s):

1. 899 - ohne Topic (POF4-899) (POF4-899)

Appears in the scientific report 2026

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Database coverage:
; ; ; Article Processing Charges ; Clarivate Analytics Master Journal List ; Current Contents - Clinical Medicine ; DOAJ Seal ; Essential Science Indicators ; Fees ; IF < 5 ; JCR ; PubMed Central ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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