von Felbert Verena, Bauerschlag Dirk, Maass Nicolai, Bräutigam Karen, Meinhold-Heerlein Ivo, Woitok Mira, Barth Stefan, Hussain Ahmad Fawzi
Department of Dermatology, University Hospital RWTH Aachen, Pauwelsstrasse 30, 52074, Aachen, Germany.
Department of Gynecology and Obstetrics, University Medical Center Schleswig-Holstein, Campus Kiel, Arnold-Heller-Strasse 3, 24105, Kiel, Germany.
J Cancer Res Clin Oncol. 2016 May;142(5):1003-11. doi: 10.1007/s00432-016-2122-7. Epub 2016 Feb 3.
The term "theranostics" represents a new paradigm in medicine especially for cancer treatment. This term was coined by Funkhouser in 2002 and defines a reagent that combines therapeutic and diagnostic properties. It is widely believed that theranostics agents will have considerable impact on healthcare before, during, and after disease by improving cancer prognosis and management simultaneously. Current theranostics approaches still rely on passive tumor targeting strategies, which have scattergun effects and tend to damage both neoplastic and non-neoplastic cells.
Here we describe a simple, controlled, and efficient method to generate homogeneous photoimmunotheranostics reagents. This method combines molecular optical imaging, photodynamic therapy, and immunotherapy using SNAP-tag technology. SNAP-tag is a derivative of the O(6)-alkylguanine-DNA alkyltransferase (AGT) which has the ability to efficiently conjugate to O(6)-benzylguanine (BG) molecules under physiological conditions depending on its folding pattern.
The theranostics agent was able to specifically recognize various epidermal growth factor receptor (EGFR)-expressing skin cancer cell lines using flow cytometry analysis and confocal microscopy and eliminate them at EC50's of 32-55 nM.
These experiments provide a framework for using SNAP-tag technology to generate homogeneous photoimmunotheranostics reagents with unified pharmacokinetic and therapeutic profiles. Furthermore, the reagent generated in this work could be used to simultaneously monitor and suppress the growth of skin squamous carcinoma and melanoma cells expressing EGFR.
“治疗诊断学”一词代表了医学领域尤其是癌症治疗方面的一种新范式。该术语由芬克豪泽于2002年创造,定义了一种兼具治疗和诊断特性的试剂。人们普遍认为,治疗诊断学试剂将通过同时改善癌症预后和管理,在疾病发生前、期间和之后对医疗保健产生重大影响。当前的治疗诊断学方法仍依赖被动肿瘤靶向策略,这种策略具有散弹枪效应,往往会对肿瘤细胞和非肿瘤细胞都造成损害。
在此,我们描述了一种简单、可控且高效的方法来生成均质的光免疫治疗诊断学试剂。该方法结合了分子光学成像、光动力疗法和使用SNAP标签技术的免疫疗法。SNAP标签是O(6)-烷基鸟嘌呤-DNA烷基转移酶(AGT)的衍生物,根据其折叠模式,它能够在生理条件下与O(6)-苄基鸟嘌呤(BG)分子高效共轭。
通过流式细胞术分析和共聚焦显微镜检查,该治疗诊断学试剂能够特异性识别各种表达表皮生长因子受体(EGFR)的皮肤癌细胞系,并在32 - 55 nM的半数有效浓度(EC50)下将其消除。
这些实验为利用SNAP标签技术生成具有统一药代动力学和治疗特性的均质光免疫治疗诊断学试剂提供了一个框架。此外,本研究中生成的试剂可用于同时监测和抑制表达EGFR的皮肤鳞状细胞癌和黑色素瘤细胞的生长。