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抗体和 Fab 片段靶向前列腺特异性膜抗原的光免疫疗法治疗前列腺癌。

Photoimmunotherapy of Prostate Cancer With Antibody and Fab Fragments Targeting the Prostate Specific Membrane Antigen.

机构信息

Department of Urology, Medical Center - University of Freiburg, Freiburg, Germany.

Faculty of Medicine, University of Freiburg, Freiburg, Germany.

出版信息

Anticancer Res. 2024 Jun;44(6):2343-2348. doi: 10.21873/anticanres.17041.


DOI:10.21873/anticanres.17041
PMID:38821609
Abstract

BACKGROUND/AIM: 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. MATERIALS AND 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. CONCLUSION: 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

背景/目的:局限性前列腺癌的标准治疗方法包括有治愈意图的前列腺切除术。然而,当肿瘤细胞残留在手术部位时,局部复发和肿瘤扩散的风险很高,导致需要进行有压力的后续治疗、生活质量受损和总体生存率降低。本研究探讨了光免疫疗法(PIT)作为前列腺癌细胞的一种新的治疗选择。

材料和方法:我们制备了由针对前列腺特异性膜抗原(PSMA)的人源化抗体或 Fab 片段与我们的硅酞菁光敏剂染料 WB692-CB1 组成的缀合物。用抗体染料或 Fab 染料缀合物孵育表达 PSMA 的前列腺癌细胞,并通过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,并通过吖啶橙染色和随后使用 Neubauer 计数室进行分析来确定细胞毒性。

结果:抗体染料缀合物以光剂量依赖性方式在前列腺癌细胞中诱导了特异性细胞毒性。用 Fab 染料缀合物处理细胞导致较低的细胞毒性,这归因于 Fab 片段结合亲和力降低和染料摄取减少。

结论:我们的新型抗体染料和 Fab 染料缀合物为局部前列腺癌患者未来的术中 PIT 提供了潜力,旨在确保从手术区域完全清除肿瘤细胞,避免局部复发,并改善临床结果。

相似文献

[1]
Photoimmunotherapy of Prostate Cancer With Antibody and Fab Fragments Targeting the Prostate Specific Membrane Antigen.

Anticancer Res. 2024-6

[2]
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J Nucl Med. 2015-1

[3]
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Cancer Genomics Proteomics. 2024

[4]
Near-Infrared Photoimmunotherapy Targeting Prostate Cancer with Prostate-Specific Membrane Antigen (PSMA) Antibody.

Mol Cancer Res. 2017-6-6

[5]
Targeting human prostate cancer with 111In-labeled D2B IgG, F(ab')2 and Fab fragments in nude mice with PSMA-expressing xenografts.

Contrast Media Mol Imaging. 2015

[6]
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[7]
PSMA-targeted bispecific Fab conjugates that engage T cells.

Bioorg Med Chem Lett. 2017-12-15

[8]
Comparison of low-molecular-weight ligand and whole antibody in prostate-specific membrane antigen targeted near-infrared photoimmunotherapy.

Int J Pharm. 2021-11-20

[9]
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[10]
A new generation of monoclonal and recombinant antibodies against cell-adherent prostate specific membrane antigen for diagnostic and therapeutic targeting of prostate cancer.

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