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针对膀胱癌的光免疫治疗的靶向 EGFR 和 HER2 的抗体-染料偶联物。

Antibody-dye Conjugates Targeting EGFR and HER2 for the Photoimmunotherapy of Bladder Cancer.

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 May;44(5):1837-1844. doi: 10.21873/anticanres.16985.


DOI:10.21873/anticanres.16985
PMID:38677753
Abstract

BACKGROUND/AIM: Although there are curative treatment options for non-muscle-invasive bladder cancer, the recurrence of this tumor is high. Therefore, novel targeted therapies are needed for the complete removal of bladder cancer cells in stages of localized disease, in order to avoid local recurrence, to spare bladder cancer patients from stressful and expensive treatment procedures and to increase their quality of life and life expectancy. This study tested a new approach for the photoimmunotherapy (PIT) of bladder cancer. MATERIALS AND METHODS: We generated a cysteine modified recombinant version of the antibody cetuximab targeting the epidermal growth factor receptor (EGFR) on the surface of bladder cancer cells. Then, we coupled the novel photoactivatable phthalocyanine dye WB692-CB1 via a maleimide linker to the free cysteines of the antibody. PIT was performed by incubating bladder cancer cells with the antibody dye conjugate followed by irradiation with visible red light. RESULTS: The conjugate was able to induce specific cytotoxicity in EGFR-positive bladder cancer cells in a light dose-dependent manner. Enhanced cytotoxicity in RT112 bladder cancer cells was evoked by addition of a second antibody dye conjugate targeting HER2 or by repeated cycles of PIT. CONCLUSION: Our new antibody dye conjugate targeting EGFR-expressing bladder cancer cells is a promising candidate for the future PIT of bladder cancer patients.

摘要

背景/目的:虽然有治疗非肌肉浸润性膀胱癌的方法,但这种肿瘤的复发率很高。因此,需要新的靶向治疗方法来彻底清除局部疾病阶段的膀胱癌细胞,以避免局部复发,使膀胱癌患者免受紧张和昂贵的治疗程序,并提高他们的生活质量和预期寿命。本研究测试了一种膀胱癌光免疫治疗(PIT)的新方法。

材料和方法:我们生成了一种针对表皮生长因子受体(EGFR)的抗体 cetuximab 的半胱氨酸修饰重组版本,该抗体靶向膀胱癌细胞表面。然后,我们通过马来酰亚胺接头将新型光活化酞菁染料 WB692-CB1 偶联到抗体的游离半胱氨酸上。通过用抗体染料缀合物孵育膀胱癌细胞,然后用可见红光照射来进行 PIT。

结果:该缀合物能够以光剂量依赖的方式诱导 EGFR 阳性膀胱癌细胞的特异性细胞毒性。通过添加针对 HER2 的第二种抗体染料缀合物或通过重复的 PIT 循环,在 RT112 膀胱癌细胞中引起了增强的细胞毒性。

结论:我们针对表达 EGFR 的膀胱癌细胞的新型抗体染料缀合物是未来膀胱癌患者 PIT 的有前途的候选物。

相似文献

[1]
Antibody-dye Conjugates Targeting EGFR and HER2 for the Photoimmunotherapy of Bladder Cancer.

Anticancer Res. 2024-5

[2]
Photoimmunotherapy of HER2-expressing Breast Cancer Cells.

Cancer Genomics Proteomics. 2024

[3]
Targeting Epidermal Growth Factor Receptor (EGFR) and Human Epidermal Growth Factor Receptor 2 (HER2) Expressing Bladder Cancer Using Combination Photoimmunotherapy (PIT).

Sci Rep. 2019-2-14

[4]
Near-Infrared Photochemoimmunotherapy by Photoactivatable Bifunctional Antibody-Drug Conjugates Targeting Human Epidermal Growth Factor Receptor 2 Positive Cancer.

Bioconjug Chem. 2017-5-17

[5]
Photoimmunotherapy of Prostate Cancer With Antibody and Fab Fragments Targeting the Prostate Specific Membrane Antigen.

Anticancer Res. 2024-6

[6]
Epidermal Growth Factor Receptor (EGFR)-targeted Photoimmunotherapy (PIT) for the Treatment of EGFR-expressing Bladder Cancer.

Mol Cancer Ther. 2017-6-15

[7]
Molecular targeted photoimmunotherapy for HER2-positive human gastric cancer in combination with chemotherapy results in improved treatment outcomes through different cytotoxic mechanisms.

BMC Cancer. 2016-1-25

[8]
Near-infrared photoimmunotherapy targeting EGFR-Shedding new light on glioblastoma treatment.

Int J Cancer. 2018-1-19

[9]
Near Infrared Photoimmunotherapy Targeting EGFR Positive Triple Negative Breast Cancer: Optimizing the Conjugate-Light Regimen.

PLoS One. 2015-8-27

[10]
Photoimmunotherapy: comparative effectiveness of two monoclonal antibodies targeting the epidermal growth factor receptor.

Mol Oncol. 2014-5

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