131I标记的人源化抗B7-H3抗体用于胶质母细胞瘤放射免疫疗法的治疗特性(英文)
作者机构：Jiangsu Institute of Clinical Immunology the First Affiliated Hospital of Soochow University State Key Laboratory of Radiation Medicine and Protection Soochow University Department of Clinical Pharmacology the First Affiliated Hospital of Soochow University Institute for Interdisciplinary Drug Research and Translational Sciences College of Pharmaceutical Sciences Soochow University Department of Hematology the First Affiliated Hospital of Soochow University Suzhou Bright Scistar Antibody Biotech.Co. Ltd.
出 版 物：《Engineering》 (工程(英文))
年 卷 期：2023年第11期
页 面：190-202页
核心收录：
学科分类：1002[医学-临床医学] 100214[医学-肿瘤学] 10[医学]
基 金：funded by the National Natural Science Foundation of China (31320103918 and 82104318) Key Research and Development Program of Jiangsu Province (BE2021644) the Jiangsu Innovative and Entrepreneurial Talent Programme(JSSCBS20211568) the Science and Technology Plan of Suzhou(SKJYD2021161 and SKY2022046) Key Project of Jiangsu Provincial Health Commission (zd2021050) the Project of State Key Laboratory of Radiation Medicine and Protection,Soochow University (GZK1202203) support of Jiangsu Institute of Nuclear Medicine for the ~(89)Zr-PET imaging in this study
摘 要：B7 homolog 3(B7-H3) has attracted much attention in glioblastoma(GBM) radioimmunotherapy(RIT)due to its abnormally high expression on tumor *** this study,we report that two specific humanized anti-human B7-H3 antibodies(hu4G4 and hu4H12) derived from mouse anti-human B7-H3 antibodies that were generated by computer-aided design and exclusively recognize membrane expression of B7-H3 by human glioma cells,Hu4G4 and hu4H12 were radiolabeled with89Zr for RIT antibody ***-positron emission tomography(PET) imaging,biodistribution and pharmacokinetic(PK) analyses of89Zr-labeled antibodies were performed in U87-xenografted models.125I labelling of the antibodies for single-photon emission computed tomography(SPECT) imaging was also used to investigate the biological behavior of the antibodies in *** rthermore,the pharmacodynamic(PD) of the131Ilabeled antibodies were evaluated in U87-xenografted mice and GL261 Red-FLuc-B7-H3 in situ glioma tumor ***-PET imaging and biodistribution analysis with a gamma counter showed that89Zr-deferoxamine(DFO)-hu4G4 had higher tumor targeting performance with lower liver uptake than89Zr-DFO-(hu4H12, immunoglobulin G(IgG)).The biodistribution results of125I-SPECT imaging were similar to those of89Zr-PET imaging,though the biodistribution in long bone joints and the thyroid *** PD analysis results indicated that131I-hu4G4 had an excellent therapeutic effect and high safety with no apparent ***,131I-hu4G4 improved the tumor vasculature in tissues with higher expression of collagen type Ⅳ and platelet-derived growth factor receptor β(PDGFR-β) compared with control treatment,as determined by immunofluorescence(IF),which contributed to inhibiting tumor *** together,our data indicate that hu4G4 exhibits good tumor targeting and specificity,achieves low nonspecific concentrations in normal tissues,and has acceptable PK characteristics.131I-hu4G4 also exerts effective antitumor effects
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