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CD11b Antibody Fragments as PET Imaging Probes for Glioma-Associated Myeloid Cells

CD11b Antibody Fragments as PET Imaging Probes for Glioma-Associated Myeloid Cells
CD11b 抗体片段作为胶质瘤相关骨髓细胞的 PET 成像探针
批准号:
9751856
负责人:
Wilson Barry Edwards
金额:
$23.42万
依托单位国家:
美国
项目类别:
财政年份:
2018
资助国家:
美国
项目状态:
已结题
起止时间:
2018-08-01 至 2020-05-31

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中文摘要
翻译
摘要 胶质母细胞瘤患者的平均生存时间保持在15个月左右,因为相对较少的有效治疗。 治疗。CD 11b+肿瘤相关髓样细胞可占肿瘤质量的40%, 已知其抑制抗肿瘤免疫并直接促进肿瘤生长。虽然取得了重大进展, 尽管在TAMC靶向治疗的开发中已经进行了大量的研究,但TAMC的分析需要分析手术治疗的结果。 切除的肿瘤组织。在这个R21应用中,我们建议开发一种新的示踪剂,Cu-64标记 抗体片段,这将允许胶质母细胞瘤中TAMC的非侵入性PET成像。因此, 验证我们的新假设,即Cu-64标记的单抗体或双抗体来源于m1/70杂交瘤 将能够定量TAMC浸润到肿瘤中并监测TAMC靶向的 免疫疗法我们将首先生成并测试注射后抗体片段的灵敏度 将来自C57 BL/6 j小鼠的不同浓度的CD 11b+小鼠脾细胞转化为CD 11b敲除的C57 BL/6 j- 背景同基因胶质瘤荷瘤小鼠(Aim 1)。然后我们将证明我们的新型抗体片段 可用于监测TAMC靶向治疗,包括抗Gr 1抗体、塞来昔布或CSF-1 R抑制剂 在GL 261同源神经胶质瘤模型和新生神经胶质瘤模型(AIM 2)中。正如m1/70克隆体可以识别的那样 无论是人类还是小鼠CD 11b,我们相信我们的临床前研究可以快速转化我们的发现, 在胶质母细胞瘤患者或其他神经炎性疾病患者中进行TAMC靶向临床试验 紊乱 !
英文摘要
ABSTRACT Average survival times for glioblastoma patients remain around 15 months because of relatively few effective treatments. CD11b+ Tumor-associated myeloid cells, can account for up to 40% of the tumor mass, are well known to suppress anti-tumor immunity, and directly promote tumor growth. While significant advances have been made in the development of TAMC-targeted therapies, analysis of TAMCs requires analysis of surgically resected tumor tissue. In this R21 application we propose that development of a novel tracer, Cu-64 labeled antibody fragments, which will allow for non-invasive PET imaging of TAMCs in glioblastomas. We will therefore, test our novel hypothesis that Cu-64-labeled monobodies or diabodies derived from the m1/70 hybridoma will enable quantification TAMC infiltration into the tumor and monitoring of TAMC-targeted immunotherapies. We will first generate and test the sensitivity of our antibody fragments following injections of varying concentrations of CD11b+ mouse spleenocytes from C57BL/6j mice into CD11b-knockout C57BL/6j- background syngeneic glioma-bearing mice (Aim 1). We will then demonstrate that our novel antibody fragments can be used to monitor TAMC-targeted therapies including anti-Gr1-antibody, Celecoxib, or a CSF-1R inhibitor in the GL261 syngeneic glioma model, and a de novo glioma model (AIM 2). As the m1/70 clone can recognize both human and mouse CD11b, we believe that our preclinical studies can lead to quick translation of our findings into TAMC-targeted clinical trials in patients with glioblastoma, or in patients with other neuroinflammatory disorders. !
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Engineered antibody fragments for PET imaging of immunotherapeutic targets in gliomas
Engineered antibody fragments for PET imaging of immunotherapeutic targets in gliomas
Engineered Antibodies as PET Probes for Monitoring Immunotherapy Responses
Engineered antibody fragments for PET imaging of immunotherapeutic targets in gliomas
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