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

被引:1
作者
Wolf, Isis [1 ,2 ,3 ]
Schultze-Seemann, Susanne [1 ,2 ]
Gratzke, Christian [1 ,2 ]
Wolf, Philipp [1 ,2 ]
机构
[1] Univ Freiburg, Med Ctr, Dept Urol, D-79106 Freiburg, Germany
[2] Univ Freiburg, Fac Med, D-79110 Freiburg, Germany
[3] Univ Freiburg, Fac Biol, D-79104 Freiburg, Germany
关键词
prostate cancer; photoimmunotherapy; CD44; EpCAM; antibody dye conjugates; MECHANISMS; ANTIGEN;
D O I
10.3390/antib14010005
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
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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页数:11
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