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 treatment 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 study, we describe the PIT of prostate cancer as novel therapeutic option for the targeted treatment of localized prostate cancer. Methods: We conjugated the new silicon phthalocyanine dye, WB692-CB2, to recombinant cysteine-modified anti-CD44 and EpCAM antibodies via a maleimide linker and tested the antibody dye conjugates for PIT on prostate cancer (PC) 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. Combinatorial treatment with both conjugates led to enhanced cytotoxic effects. Conclusions: WB692-CB2-based PIT can serve as an effective focal therapy, 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 lead to the prevention of local recurrence after RP and thus to the complete cure of PC patients.