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细菌磁小体-抗4-1BB抗体复合物的制备及其抗肿瘤效率评估:从格氏嗜盐碱螺旋菌中分离得到的作为抗体载体的细菌磁小体。

Preparation and anti-tumor efficiency evaluation of bacterial magnetosome-anti-4-1BB antibody complex: Bacterial magnetosome as antibody carriers isolated from Magnetospirillum gryphiswaldense.

作者信息

Tang Yi-Shu, Wang Dongmei, Zhou Chunxia, Zhang Shuren

机构信息

Department of Laboratory Medicine, The First Affiliated Hospital of Chongqing Medical University, Chongqing, People's Republic of China.

Department of Immunology, Cancer Institute and Cancer Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, People's Republic of China.

出版信息

Biotechnol Appl Biochem. 2019 May;66(3):290-297. doi: 10.1002/bab.1724. Epub 2019 Jan 11.

Abstract

Bacterial magnetosomes (BMs) are used as carriers for antibodies, enzymes, and nucleic acids. This study aimed to demonstrate the clinical utility of BMs derived from Magnetospirillum gryphiswaldense for use in anti-tumor immunotherapy. Bis(sulfosuccinimidyl) suberate (BS3) was used to prepare BM-anti-4-1BB antibody complexes. We used syngeneic TC-1 mouse models of cancer to investigate whether BMs combined with an anti-4-1BB agonistic antibodies could enhance the therapeutic effects of anti-4-1BB antibodies in localized disease settings. Anti-4-1BB antibodies were combined with purified BMs at a concentration of 168 mg antibody per milligram BM (mg IgG/mg BM) using BS3. The anti-4-1BB antibody-coupled BMs (BM-Ab complexes) and control BMs displayed similar morphologies and measurements when examined by transmission electron microscope (TEM). In a mouse tumor model, intravenous injection of BM-Abs combined with magnetic treatment resulted in greater tumor protection than did other treatment methods (P < 0.05). These results demonstrate the in vivo anti-tumor properties of BM-Abs complexes. The coupling of anti-4-1BB antibodies to magnetosomes may have potential for clinical application to antitumor antibody therapy.

摘要

细菌磁小体(BMs)被用作抗体、酶和核酸的载体。本研究旨在证明源自格氏嗜盐碱螺旋菌的磁小体在抗肿瘤免疫治疗中的临床应用价值。使用辛二酸双(磺基琥珀酰亚胺酯)(BS3)制备磁小体-抗4-1BB抗体复合物。我们使用同基因TC-1小鼠癌症模型来研究磁小体与抗4-1BB激动性抗体联合使用是否能增强抗4-1BB抗体在局部疾病环境中的治疗效果。使用BS3将抗4-1BB抗体与纯化的磁小体以每毫克磁小体168毫克抗体(毫克IgG/毫克磁小体)的浓度进行结合。通过透射电子显微镜(TEM)检查时,抗4-1BB抗体偶联的磁小体(磁小体-抗体复合物)和对照磁小体显示出相似的形态和尺寸。在小鼠肿瘤模型中,静脉注射磁小体-抗体并结合磁疗比其他治疗方法产生了更大的肿瘤保护作用(P < 0.05)。这些结果证明了磁小体-抗体复合物的体内抗肿瘤特性。抗4-1BB抗体与磁小体的偶联可能在抗肿瘤抗体治疗的临床应用中具有潜力。

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