Targeting CD44 and EpCAM with Antibody Dye Conjugates for the Photoimmunotherapy of Prostate Cancer

Background/Objectives: Photoimmunotherapy (PIT) is an innovative approach for the targeted therapy of cancer. In PIT, photosensitizer dyes are conjugated to tumor-specific antibodies for targeted delivery into cancer cells. Upon irradiation with visible light, the photosensitizer dye is activated an...

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Main Authors: Isis Wolf, Susanne Schultze-Seemann, Christian Gratzke, Philipp Wolf
Format: Article
Language:English
Published: MDPI AG 2025-01-01
Series:Antibodies
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Online Access:https://www.mdpi.com/2073-4468/14/1/5
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author Isis Wolf
Susanne Schultze-Seemann
Christian Gratzke
Philipp Wolf
author_facet Isis Wolf
Susanne Schultze-Seemann
Christian Gratzke
Philipp Wolf
author_sort Isis Wolf
collection DOAJ
description Background/Objectives: Photoimmunotherapy (PIT) is an innovative approach for the targeted therapy of cancer. In PIT, photosensitizer dyes are conjugated to tumor-specific antibodies for targeted delivery into cancer cells. Upon irradiation with visible light, the photosensitizer dye is activated and induces cancer-specific cell death. In the present article, we describe the PIT of prostate cancer (PC) as a therapeutic option for the targeted treatment of localized prostate cancer. Methods: We conjugated the silicon phthalocyanine dye WB692-CB2 to recombinant cysteine-modified anti-CD44 and anti-EpCAM antibodies via a maleimide linker and tested the antibody dye conjugates for PIT on PC cells and prostate cancer stem cell (PCSC)-like cells. Results: The anti-CD44 and anti-EpCAM antibody dye conjugates showed specific binding and high cytotoxicity against PC and PCSC-like cells following irradiation with red light. Combined treatment with both conjugates led to enhanced cytotoxic effects. Conclusions: PIT with our dye WB692-CB2 can serve as an effective focal therapy against prostate cancer, preserving the prostate gland and minimizing side effects. It can be employed during radical prostatectomy (RP) to treat residual tumor cells or lymph node metastases in areas where further surgical intervention is not feasible. Utilizing multiple conjugates against antigens expressed on differentiated PC and PCSC-like cells, such as CD44 and EpCAM, could be an effective method to eradicate residual cancer cells in heterogeneous tumors. This approach could reduce the risk of local recurrence after RP and thus increase the therapeutic outcome of PC patients.
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spelling doaj-art-0b721d9e38f54509b2dcf8cd4f3948972025-08-20T03:40:43ZengMDPI AGAntibodies2073-44682025-01-01141510.3390/antib14010005Targeting CD44 and EpCAM with Antibody Dye Conjugates for the Photoimmunotherapy of Prostate CancerIsis Wolf0Susanne Schultze-Seemann1Christian Gratzke2Philipp Wolf3Department of Urology, Medical Center—University of Freiburg, 79106 Freiburg im Breisgau, GermanyDepartment of Urology, Medical Center—University of Freiburg, 79106 Freiburg im Breisgau, GermanyDepartment of Urology, Medical Center—University of Freiburg, 79106 Freiburg im Breisgau, GermanyDepartment of Urology, Medical Center—University of Freiburg, 79106 Freiburg im Breisgau, GermanyBackground/Objectives: Photoimmunotherapy (PIT) is an innovative approach for the targeted therapy of cancer. In PIT, photosensitizer dyes are conjugated to tumor-specific antibodies for targeted delivery into cancer cells. Upon irradiation with visible light, the photosensitizer dye is activated and induces cancer-specific cell death. In the present article, we describe the PIT of prostate cancer (PC) as a therapeutic option for the targeted treatment of localized prostate cancer. Methods: We conjugated the silicon phthalocyanine dye WB692-CB2 to recombinant cysteine-modified anti-CD44 and anti-EpCAM antibodies via a maleimide linker and tested the antibody dye conjugates for PIT on PC cells and prostate cancer stem cell (PCSC)-like cells. Results: The anti-CD44 and anti-EpCAM antibody dye conjugates showed specific binding and high cytotoxicity against PC and PCSC-like cells following irradiation with red light. Combined treatment with both conjugates led to enhanced cytotoxic effects. Conclusions: PIT with our dye WB692-CB2 can serve as an effective focal therapy against prostate cancer, preserving the prostate gland and minimizing side effects. It can be employed during radical prostatectomy (RP) to treat residual tumor cells or lymph node metastases in areas where further surgical intervention is not feasible. Utilizing multiple conjugates against antigens expressed on differentiated PC and PCSC-like cells, such as CD44 and EpCAM, could be an effective method to eradicate residual cancer cells in heterogeneous tumors. This approach could reduce the risk of local recurrence after RP and thus increase the therapeutic outcome of PC patients.https://www.mdpi.com/2073-4468/14/1/5prostate cancerphotoimmunotherapyCD44EpCAMantibody dye conjugates
spellingShingle Isis Wolf
Susanne Schultze-Seemann
Christian Gratzke
Philipp Wolf
Targeting CD44 and EpCAM with Antibody Dye Conjugates for the Photoimmunotherapy of Prostate Cancer
Antibodies
prostate cancer
photoimmunotherapy
CD44
EpCAM
antibody dye conjugates
title Targeting CD44 and EpCAM with Antibody Dye Conjugates for the Photoimmunotherapy of Prostate Cancer
title_full Targeting CD44 and EpCAM with Antibody Dye Conjugates for the Photoimmunotherapy of Prostate Cancer
title_fullStr Targeting CD44 and EpCAM with Antibody Dye Conjugates for the Photoimmunotherapy of Prostate Cancer
title_full_unstemmed Targeting CD44 and EpCAM with Antibody Dye Conjugates for the Photoimmunotherapy of Prostate Cancer
title_short Targeting CD44 and EpCAM with Antibody Dye Conjugates for the Photoimmunotherapy of Prostate Cancer
title_sort targeting cd44 and epcam with antibody dye conjugates for the photoimmunotherapy of prostate cancer
topic prostate cancer
photoimmunotherapy
CD44
EpCAM
antibody dye conjugates
url https://www.mdpi.com/2073-4468/14/1/5
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AT christiangratzke targetingcd44andepcamwithantibodydyeconjugatesforthephotoimmunotherapyofprostatecancer
AT philippwolf targetingcd44andepcamwithantibodydyeconjugatesforthephotoimmunotherapyofprostatecancer