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ORIGINAL RESEARCH article

Front. Oncol.

Sec. Cancer Immunity and Immunotherapy

PSCA-directed nanosized bio-immune conjugates (NANO:BICs) enable selective uptake of TLR9 agonists in bladder cancer cells

Provisionally accepted
Max IltzscheMax Iltzsche1Nancy WetterlingNancy Wetterling2Lissy JilekLissy Jilek2Daniel NahhasDaniel Nahhas1Marlena HesseMarlena Hesse1Stefanie TietzeStefanie Tietze2Achim TemmeAchim Temme2,3,4Christian ThomasChristian Thomas1Susanne FuesselSusanne Fuessel1Barbara KindBarbara Kind1*
  • 1Department of Urology, Carl Gustav Carus Faculty of Medicine, Dresden University of Technology, Dresden, Dresden, Germany, Dresden, Germany
  • 2Department of Neurosurgery, Section Experimental Neurosurgery and Tumor Immunology, University Hospital Dresden, Dresden, Germany, Dresden, Germany
  • 3German Cancer Consortium (DKTK), Dresden, Germany; German Cancer Research Center (DKFZ), Heidelberg, Germany, Dresden, Germany
  • 4National Center for Tumor Diseases Dresden, Dresden, Germany, Dresden, Germany

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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. This study demonstrates that prostate stem cell antigen (PSCA), frequently overexpressed in BCa, can be effectively targeted for the delivery of immunomodulatory agents. Using nanosized bio-immune conjugates (NANO:BICs) comprising a single-chain antibody (scFv) against PSCA and CpG-oligodeoxynucleotides (ODN) as TLR9 agonists, we achieved selective uptake of CpG-ODN-loaded nanoparticles in PSCA-positive BCa cells. The targeted delivery was confirmed through fluorescence-based quantification, which revealed a specific internalization of the nanoparticles via PSCA receptors. 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.

Keywords: Bladder cancer, Fluorescence intensity analysis, Immunotherapy, NANO:BICs, NMIBC, PSCA, Single-Chain Antibodies, targeted therapy

Received: 04 Nov 2025; Accepted: 20 Jan 2026.

Copyright: © 2026 Iltzsche, Wetterling, Jilek, Nahhas, Hesse, Tietze, Temme, Thomas, Fuessel and Kind. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Barbara Kind

Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.

Supplementary Material