Lighting the way to cancer cell destruction: photoimmunotherapy of prostate cancer & prostate cancer stem cells

Abstract: Prostate cancer (PC) represents one of the most prevalent malignancies in men, with successful treatment critically dependent on the complete eradication of the tumor to prevent relapse and metastasis. Despite advancements in PC therapies, tumor heterogeneity driven by cancer stem cells and the persistence of residual tumor cells in surgical margins frequently results in biochemical relapse. Consequently, novel approaches targeting both PC and PC stem cells are urgently needed to improve therapeutic outcomes and prevent disease progression. Photoimmunotherapy (PIT) is an innovative cancer treatment that combines monoclonal antibodies with lightactivatable photosensitizers (PSs) to selectively induce cancer cell death upon irradiation with non-ionizing red light, thereby minimizing off-target effects and preserving adjacent healthy tissues. In this study, we evaluated the silicon phthalocyanine dye WB692-CB2 as a PS for the PIT of PC, which is the first lightactivatable PS that can be conjugated site-specific via a maleimide linker to cysteines. We conjugated WB692-CB2 to humanized antibodies with engineered cysteine mutations in their heavy chains. These antibodies specifically target PSMA, CD44 or EpCAM on PC or PC stem-like cells. The resulting antibody-PS conjugates exhibited high affinity and specificity towards antigen-positive cells and induced rapid cell death following irradiation with red light. Moreover, additive effects were observed when two different antigens on the same cell were targeted by PIT. Treated cells exhibited morphological characteristics associated with pyroptosis. Mechanistic studies revealed the generation of reactive oxygen species, triggering a cascade of intracellular events involving lipid peroxidation, caspase-1 activation, gasdermin D cleavage and membrane rupture followed by release of pro-inflammatory cellular contents. In first in vivo experiments, PIT resulted in a significant reduction of tumor growth and enhanced overall survival in mice bearing subcutaneous prostate tumor xenografts. In conclusion, our study highlights the potential of the novel phthalocyanine dye WB692- CB2 as PS for the fluorescence-based detection and PIT of cancer. By effectively targeting PC and PC stem cells, and inducing systemic anti-tumor immune response by induction of pyroptosis, this approach holds significant promise for improving therapeutic outcomes in PC patients in future clinical applications

Object Details

• Location: Deutsche Nationalbibliothek Frankfurt am Main
• Extent: Online-Ressource
• Language: Englisch
• Notes: Universität Freiburg, Dissertation, 2024

Classification and Topics

• Keyword: Prostatakrebs ; Krebs

Contributors, Places and Time

• Event: Veröffentlichung
• (where): Freiburg
• (who): Universität
• (when): 2024
• Creator: Wolf, Isis
• Contributor: Martin, Stefan F. ; Wolf, Philipp ; Zeiser, Robert ; Albert-Ludwigs-Universität Freiburg. Fakultät für Biologie ; Universitätsklinikum Freiburg ; Albert-Ludwigs-Universität Freiburg. Medizinische Fakultät ; Universitätsklinikum Freiburg. Klinik für Urologie

Further information

• DOI: 10.6094/UNIFR/258506
• URN: urn:nbn:de:bsz:25-freidok-2585066
• Rights: Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.
• Last update: 15.08.2025, 7:24 AM CEST