Abstract：
OBJECTIVE: The standard treatment for localized prostate cancer involves surgical removal of the prostate with curative intent. However, when tumor cells persist in the operation site, there is high risk of local recurrence and tumor spread, leading to stressful follow-up treatments, impaired quality of life, and reduced overall survival. This study examined photoimmunotherapy (PIT) as a new treatment option for prostate cancer cells.
METHODS: We generated conjugates consisting of either a humanized antibody or Fab fragments thereof targeting the prostate specific membrane antigen (PSMA), along with our silicon phthalocyanine photosensitizer dye WB692-CB1. PSMA-expressing prostate cancer cells were incubated with the antibody dye or Fab dye conjugates and cell binding was measured using flow cytometry. Cells were irradiated with varying doses of red light for dye activation, and cytotoxicity was determined by erythrosin B staining and subsequent analysis using a Neubauer counting chamber.
RESULTS: Specific cytotoxicity was induced with the antibody dye conjugate in the prostate cancer cells in a light dose-dependent manner. Treatment of the cells with the Fab dye conjugate resulted in lower cytotoxicity, which could be attributed to a reduced binding affinity and a reduced dye uptake of the Fab fragment.
CONCLUSIONS: Our new antibody dye and Fab dye conjugates offer potential for future intraoperative PIT in patients with localized prostate cancer, with the aim to ensure complete removal of tumor cells from the surgical area, to avoid local recurrence, and to improve clinical outcome.
METHODS: We generated conjugates consisting of either a humanized antibody or Fab fragments thereof targeting the prostate specific membrane antigen (PSMA), along with our silicon phthalocyanine photosensitizer dye WB692-CB1. PSMA-expressing prostate cancer cells were incubated with the antibody dye or Fab dye conjugates and cell binding was measured using flow cytometry. Cells were irradiated with varying doses of red light for dye activation, and cytotoxicity was determined by erythrosin B staining and subsequent analysis using a Neubauer counting chamber.
RESULTS: Specific cytotoxicity was induced with the antibody dye conjugate in the prostate cancer cells in a light dose-dependent manner. Treatment of the cells with the Fab dye conjugate resulted in lower cytotoxicity, which could be attributed to a reduced binding affinity and a reduced dye uptake of the Fab fragment.
CONCLUSIONS: Our new antibody dye and Fab dye conjugates offer potential for future intraoperative PIT in patients with localized prostate cancer, with the aim to ensure complete removal of tumor cells from the surgical area, to avoid local recurrence, and to improve clinical outcome.
摘要：
目的：局限性前列腺癌的标准治疗包括手术切除前列腺。然而,当肿瘤细胞持续存在于手术部位时，局部复发和肿瘤扩散的风险很高，导致紧张的后续治疗，生活质量受损，降低总体生存率。这项研究检查了光免疫疗法（PIT）作为前列腺癌细胞的新治疗选择。
方法：我们产生了由靶向前列腺特异性膜抗原（PSMA）的人源化抗体或其Fab片段组成的缀合物，以及我们的硅酞菁光敏剂染料WB692-CB1。将表达PSMA的前列腺癌细胞与抗体染料或Fab染料缀合物一起孵育,并使用流式细胞术测量细胞结合。用不同剂量的红光照射细胞以激活染料，和细胞毒性通过红色素B染色和随后使用Neubauer计数室的分析来确定。
结果:用抗体染料缀合物在前列腺癌细胞中以光剂量依赖性方式诱导特异性细胞毒性。用Fab染料缀合物处理细胞导致较低的细胞毒性,这可归因于Fab片段的降低的结合亲和力和降低的染料摄取。
结论：我们的新抗体染料和Fab染料缀合物提供了未来局部前列腺癌患者术中PIT的潜力，为了确保从手术区域完全去除肿瘤细胞，为了避免局部复发，并改善临床结果。
方法：我们产生了由靶向前列腺特异性膜抗原（PSMA）的人源化抗体或其Fab片段组成的缀合物，以及我们的硅酞菁光敏剂染料WB692-CB1。将表达PSMA的前列腺癌细胞与抗体染料或Fab染料缀合物一起孵育,并使用流式细胞术测量细胞结合。用不同剂量的红光照射细胞以激活染料，和细胞毒性通过红色素B染色和随后使用Neubauer计数室的分析来确定。
结果:用抗体染料缀合物在前列腺癌细胞中以光剂量依赖性方式诱导特异性细胞毒性。用Fab染料缀合物处理细胞导致较低的细胞毒性,这可归因于Fab片段的降低的结合亲和力和降低的染料摄取。
结论：我们的新抗体染料和Fab染料缀合物提供了未来局部前列腺癌患者术中PIT的潜力，为了确保从手术区域完全去除肿瘤细胞，为了避免局部复发，并改善临床结果。
