In vivo endoscopic molecular imaging to predict therapeutic response to anti-adhesion molecule therapy in Crohn's disease patients

体内内窥镜分子成像预测克罗恩病患者对抗粘连分子治疗的治疗反应

• 批准号: 273812327
• 负责人: Professor Dr. Raja Atreya
• 金额: --
• 依托单位: Medizinische Klinik 1 - Gastroenterologie, Pneumologie und Endokrinologie
• 依托单位国家: 德国
• 项目类别: Clinical Research Units
• 财政年份: 2015
• 资助国家: 德国
• 起止时间: 2014-12-31 至 2018-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/273812327?language=en
• 关键词: vivo; endoscopic; molecular; imaging; predict

The advent of biological therapies has greatly enhanced our therapeutic possibilities In Crohn's disease patients. However, about 40% do not respond to these agents. It is therefore of high clinical relevance to find a predictor for response to biological treatment. In a previous study we demonstrated that topical administration of a fluorescent anti-TNF antibody led to the detection of Intestinal mTNF+ Immune cells during confocal laser endomicroscopy. Patients with high amounts of mTNF+ cells showed significantly higher response upon subsequent anti-TNF therapy compared to patients with low amounts of mTNF+ cells. Aim of the proposed study is the in vivo visualization of a4ß7 bearing mucosal cells in Crohn's disease patients by an endoscopic molecular Imaging procedure with a fluorescent ant-adhesion molecule antibody directed against the a4ß7 integrin. The amount of a4ß7+ cells will be correlated to the clinical response to therapy with an antl-a4ß7 antibody and might serve as a predictive biomarker regarding therapeutic efficacy. These data could further indicate that molecular imaging with fluorescent antibodies has the potential to predict therapeutic responses to biological treatments and open new avenues for personalized medicine in Crohn's disease.

生物疗法的出现大大提高了我们对克罗恩病患者的治疗可能性。然而，大约40%的人对这些药物没有反应。因此，找到生物治疗反应的预测因子具有高度的临床意义。在先前的研究中，我们证明了局部施用荧光抗TNF抗体导致在共聚焦激光显微内镜检查期间检测肠mTNF+免疫细胞。与低mTNF+细胞量的患者相比，高mTNF+细胞量的患者在后续抗TNF治疗后显示出显著更高的应答。本研究的目的是通过使用针对α 4 β 7整联蛋白的荧光抗粘附分子抗体的内窥镜分子成像程序，对克罗恩病患者中带有α 4 β 7的粘膜细胞进行体内显像。α 4 β 7+细胞的量将与对抗1-α 4 β 7抗体治疗的临床反应相关，并且可以作为关于治疗功效的预测性生物标志物。这些数据可能进一步表明，荧光抗体分子成像有可能预测对生物治疗的治疗反应，并为克罗恩病的个性化治疗开辟新的途径。