Biotechnology R&D Alfasigma SpA, Via Pontina, Km 30.400, 00071 Pomezia, Italy.
Biotechnology R&D Alfasigma SpA, Via Pontina, Km 30.400, 00071 Pomezia, Italy.
Bioorg Med Chem. 2019 Aug 1;27(15):3248-3253. doi: 10.1016/j.bmc.2019.05.047. Epub 2019 May 31.
Tenatumomab is an anti-tenascin murine monoclonal antibody previously used in clinical trials for delivering radionuclides to tumors by both pre-targeting (biotinylated Tenatumomab within PAGRIT) and direct Iodine labeling approaches. Here we present the synthesis and in vitro characterization of three Tenatumomab conjugates to bifunctional chelating agents (NHS-DOTA, NCS-DOTA and NCS-DTPA). Results indicate ST8198AA1 (Tenatumomab-DOTAMA, derived by conjugation of NHS-DOTA), as the most promising candidate in terms of conjugation rate and yield, stability, antigen immunoreactivity and affinity. Labeling efficiency of the different chelators was investigated with a panel of cold metals indicating DOTAMA as the best chelator. Labeling of Tenatumomab-DOTAMA was then optimized with several metals and stability performed confirms suitability of this conjugate for further development. ST8198AA1 represents an improvement of the previous antibody forms because the labeling with radionuclides like Lu or Cu would allow theranostic applications in patients bearing tenascin expressing tumors.
替妥莫单抗是一种抗 tenascin 的鼠单克隆抗体，以前曾在临床试验中用于通过预靶向（PAGRIT 中的生物素化替妥莫单抗）和直接碘标记方法将放射性核素递送至肿瘤。在这里，我们介绍了三种替妥莫单抗与双功能螯合剂（NHS-DOTA、NCS-DOTA 和 NCS-DTPA）的缀合物的合成和体外表征。结果表明，ST8198AA1（Tenatumomab-DOTAMA，通过 NHS-DOTA 缀合得到）是最有前途的候选物，因为它具有缀合率和产率、稳定性、抗原免疫反应性和亲和力方面的优势。用一组冷金属研究了不同螯合剂的标记效率，结果表明 DOTAMA 是最好的螯合剂。然后优化了 Tenatumomab-DOTAMA 的标记条件，并进行了稳定性研究，证实了该缀合物适合进一步开发。ST8198AA1 是对以前的抗体形式的改进，因为用放射性核素如 Lu 或 Cu 进行标记将允许在表达 tenascin 的肿瘤患者中进行治疗诊断应用。
