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Inducible B-regulatory cells (iBREGs) for treatment of Multiple Sclerosis

用于治疗多发性硬化症的诱导型 B 调节细胞 (iBREG)

基本信息

批准号：
9434646
负责人：
Jacques Galipeau
金额：
$ 29.14万
依托单位：
UNIVERSITY OF WISCONSIN-MADISON
依托单位国家：
美国
项目类别：
财政年份：
2011
资助国家：
美国
起止时间：
2011-12-01 至 2018-11-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9434646
关键词：
Inducible regulatory cells iBREGs treatment

项目摘要

DESCRIPTION (provided by applicant): We have generated a completely new class of immune suppressive agents based on a GMCSF and IL15 synthetic protein we called GIFT15. We've validated its use in mice and have further demonstrated that this compound promotes development of inducible B-regulatory cells (aka as iBregs) which leads to remission of EAE in mice. Therefore, the funding of this study will enable us to better understand the mechanism of action of iBregs and GIFT15 in the treatment of EAE. We will also define the safest and most efficient use of iBregs and recombinant GIFT15. In addition, we have generated the human version of GIFT15 and demonstrated its suppressive potential on human immune cells. As an additional step, validation of the mouse cell therapy approach will be achieved using human immune cells collected from MS patients, ex vivo treated with the human GIFT15. Assuming that iBregs or GIFT15 protein therapy leads to clinical benefit with an acceptable toxicity profile in EAE mice, the translational use of the human ortholog of GIFT15 in phase I/II clinical studies could be rapidly initiated based on this pre-clinical work. Indeed, the use of rGIFT15 in the context of MS as part of a therapeutic treatment will serve as the basis for the adoption and validation of this approach for a variety of diseases such as inflammatory bowel disease (IBD), graft-versus-host disease (GVHD), rheumatoid arthritis (RA) or even in the context of cell and organ transplantations. Thus, the utility of the GIFT15 compound as a way to generate suppressive cells in vitro and likely in vivo represents an approach with a wide array of clinical applications for catastrophic illnesses with unmet medical needs, especially MS. In sum, this study will enable us to pursue the characterization of iBregs and GIFT15 protein pharmacological product and will serve as rational for human clinical studies.

描述（由申请人提供）：我们已经产生了一类全新的免疫抑制剂，其基于我们称为GIFT 15的GMCSF和IL 15合成蛋白。我们已经验证了它在小鼠中的用途，并进一步证明了这种化合物促进诱导型B调节细胞（又名iBAE）的发育，从而导致小鼠EAE的缓解。因此，这项研究的资助将使我们能够更好地了解iB和GIFT 15治疗EAE的作用机制。我们还将确定最安全和最有效地使用iBclase和重组GIFT 15。此外，我们已经产生了GIFT 15的人类版本，并证明了其对人类免疫细胞的抑制潜力。作为额外步骤，将使用从MS患者收集的人免疫细胞实现小鼠细胞治疗方法的验证，所述MS患者用人GIFT 15离体处理。假设iBclad或GIFT 15蛋白治疗在EAE小鼠中产生临床益处，具有可接受的毒性特征，基于该临床前工作，可以快速启动GIFT 15的人直系同源物在I/II期临床研究中的翻译使用。事实上，在MS的背景下使用rGIFT 15作为治疗性治疗的一部分将作为采用和验证该方法用于多种疾病的基础，所述疾病例如炎性肠病（IBD）、移植物抗宿主病（GVHD）、类风湿性关节炎（RA）或甚至在细胞和器官移植的背景下。因此，GIFT 15化合物作为在体外和可能在体内产生抑制性细胞的方式的效用代表了一种具有广泛临床应用的方法，用于具有未满足的医疗需求的灾难性疾病，特别是MS。总之，本研究将使我们能够追求iBcl 2和GIFT 15蛋白药理学产物的表征，并将作为人类临床研究的合理性。