A novel pancreatic β-cell targeting bispecific-antibody (BsAb) can prevent the development of type 1 diabetes in NOD mice.
A novel pancreatic β-cell targeting bispecific-antibody (BsAb) can prevent the development of type 1 diabetes in NOD mice.
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一种新型的胰腺β细胞靶向双特异性抗体（BSAB）可以防止NOD小鼠中1型糖尿病的发展。
DOI：
10.1016/j.clim.2014.04.014
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发表时间：
2014-07
期刊：
影响因子：
--
通讯作者：
Prabhakar BS
中科院分区：
文献类型：
--
作者：
Bhattacharya P;Fan J;Haddad C;Essani A;Gopisetty A;Elshabrawy HA;Vasu C;Prabhakar BS
为了制备一种新的双特异性抗体（BsAb）作为T1 D的潜在靶向治疗，我们制备了针对β细胞上表达的葡萄糖转运蛋白-2（GLUT-2）的“功能惰性”单克隆抗体（mAb）以用作锚定抗体。治疗臂是针对细胞毒性T淋巴细胞抗原4（CTLA-4）的激动性mAb，CTLA-4是在活化的CD 4 + T细胞上表达的T细胞活化的负调节剂。通过将抗GLUT 2 mAb化学偶联至激动性抗CTLA-4 mAb来制备BsAb。该BsAb能够在体外与GLUT 2和CTLA-4结合，并且在体外和体内与胰岛结合。我们通过治疗非肥胖糖尿病（NOD）小鼠测试了这种BsAb的安全性和有效性，发现它可以延迟糖尿病的发作，没有明显的不良副作用。因此，CTLA-4对来自靶组织的活化T细胞的参与可以是治疗1型糖尿病的有效方法。
To prepare a novel Bispecific Antibody (BsAb) as a potential targeted therapy for T1D, we produced a “functionally inert” monoclonal antibody (mAb) against Glucose transporter-2 (GLUT-2) expressed on β-cells to serve as an anchoring antibody. The therapeutic arm is an agonistic mAb against Cytotoxic T-Lymphocyte Antigen 4 (CTLA-4), a negative regulator of T-cell activation expressed on activated CD4+ T-cells. A BsAb was prepared by chemically coupling an anti-GLUT2 mAb to an agonistic anti-CTLA-4 mAb. This BsAb was able to bind to GLUT2 and CTLA-4 in vitro, and to pancreatic islets, both in vitro and in vivo. We tested the safety and efficacy of this BsAb by treating Non-Obese Diabetes (NOD) mice and found that it could delay the onset of diabetes with no apparent undesirable side effects. Thus, engagement of CTLA-4 on activated T cells from target tissue can be an effective way to treat type-1 diabetes.
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影响因子：
4.4
作者：
Li, Ruobing;Perez, Nicolas;Vasu, Chenthamarakshan
通讯作者：
Vasu, Chenthamarakshan
影响因子：
4.4
作者：
Masteller, EL;Warner, MR;Bluestone, JA
通讯作者：
Bluestone, JA
影响因子：
7.7
作者：
Alard, Pascale;Manirarora, Jean N.;Kosiewicz, Michele M.
通讯作者：
Kosiewicz, Michele M.
影响因子：
56.9
作者：
LINSLEY, PS;WALLACE, PM;TEPPER, MA
通讯作者：
TEPPER, MA
DOI：
10.1084/jem.20051409
发表时间：
2005-11-21
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Chen Z;Herman AE;Matos M;Mathis D;Benoist C
通讯作者：
Benoist C