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一种新型化学设计的(Globo)3-DTPA-KLH抗原的合成与表征

Synthesis and characterization of a novel chemically designed (Globo)3-DTPA-KLH antigen.

作者信息

Hajmohammadi Mehdi, Siadat Seyed Davar, Ghorbani Masoud, Shafiee Ardestani Mehdi, Teimourian Shahram, Asgari Vahid, Ahangari Cohan Reza, Hajmohammadi Mostafa, Hajmohammadi Akram, Behzadi Ramezan, Rajab Nezhad Saied, Namvar Asl Nabiollah

机构信息

Department of Research and Biotechnology, Pasteur Institute of Iran, Tehran, Iran.

Department of Microbiology, Pasteur Institute of Iran, Tehran, Iran.

出版信息

Drug Des Devel Ther. 2014 Dec 22;9:217-39. doi: 10.2147/DDDT.S72530. eCollection 2015.

Abstract

In recent years, many experiments have been conducted for the production and evaluation of anticancer glycoconjugated vaccines in developed countries and many achievements have been accomplished with Globo H derivatives. In the current experiment, a new chemically designed triplicate version of (Globo H)3-diethylenetriamine pentaacetic acid (DTPA)-KLH antigen was synthesized and characterized. Immunization with (Globo H)3-DTPA-KLH, a hexasaccharide that is a member of a family of antigenic carbohydrates that are highly expressed in various types of cancers conjugated with DTPA and KLH protein, induced a high level of antibody titer along with an elevated level of IL-4 in mice. Treatment of tumors with the collected sera from immunized mice decreased the tumor size in nude mice as well. None of the immunized mice illustrated any sign of tumor growth after injection of MCF-7 cells compared to the control animals. These findings, based on the newly presented structure of the Globo H antigen, lend exciting and promising evidence for clinical advancement in the development of a therapeutic vaccine in the future.

摘要

近年来,发达国家开展了许多关于抗癌糖缀合物疫苗生产和评估的实验,并且在Glob H衍生物方面取得了许多成果。在当前实验中,合成并表征了一种新的化学设计的三联体版本的(Glob H)3-二乙烯三胺五乙酸(DTPA)-钥孔血蓝蛋白(KLH)抗原。用(Glob H)3-DTPA-KLH免疫小鼠,(Glob H)3-DTPA-KLH是一种六糖,属于在各种类型癌症中高表达的抗原性碳水化合物家族成员,与DTPA和KLH蛋白偶联,诱导了高水平的抗体滴度以及小鼠体内IL-4水平的升高。用免疫小鼠收集的血清处理肿瘤也减小了裸鼠的肿瘤大小。与对照动物相比,注射MCF-7细胞后,没有一只免疫小鼠出现肿瘤生长的迹象。基于新呈现的Glob H抗原结构的这些发现,为未来治疗性疫苗开发的临床进展提供了令人兴奋且充满希望的证据。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4324/4278734/8dde247d1d5c/dddt-9-217Fig1.jpg

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