T Cell Delivery of Nanoparticles-Bound Anti-CD20 Monoclonal Antibody: Successful B Cell Depletion in the Spinal Cord during Experimental Autoimmune Encephalomyelitis

T Cell Delivery of Nanoparticles-Bound Anti-CD20 Monoclonal Antibody: Successful B Cell Depletion in the Spinal Cord during Experimental Autoimmune Encephalomyelitis
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DOI:
10.1007/s11481-020-09931-w
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发表时间:
2020-06-09
影响因子:
6.2
通讯作者:
Ballerini, Clara
Ballerini, Clara
中科院分区:
医学3区
文献类型:
--
作者:
Carnasciali, Alberto;Amoriello, Roberta;Ballerini, Clara

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我们开发了一种基于纳米技术的细胞介导的药物递送系统,通过将与抗CD 20单克隆抗体结合的纳米颗粒负载于髓鞘抗原特异性T细胞。抗CD 20抗体是目前治疗多发性硬化症(MS)的药物(ocrelizumab),多发性硬化症是中枢神经系统(CNS)的一种慢性、炎症性和自身免疫性疾病。CD 20耗竭与活动性复发和进展性MS的疗效相关,但可能无法有效靶向CNS中的炎性细胞。在我们的工作中,在小鼠中静脉内转移含有纳米颗粒-抗-CD 20复合物的T细胞导致脾和脑中的B细胞耗竭,而单独注射抗-CD 20仅耗竭脾中的B细胞。在实验性自身免疫性脑脊髓炎(EAE)(MS的动物模型)中测试该系统,我们发现脊髓B细胞耗竭改善了疾病过程和病理。
We developed a nanotechnology based-cell mediated drug delivery system by loading myelin antigen-specific T cells with nanoparticles bound to anti-CD20 monoclonal antibody. Anti-CD20 antibody is a current treatment (ocrelizumab) for multiple sclerosis (MS), a chronic, inflammatory and autoimmune disease of the central nervous system (CNS). CD20-depletion has been associated with efficacy in active relapsing and progressive MS, but may not efficiently target inflammatory cells compartmentalized in the CNS. In our work, the intravenous transfer of T cells containing nanoparticle-anti-CD20 complex in mice causes B cell depletion in the spleen and in the brain, whereas the injection of anti-CD20 alone depletes B cells only in the spleen. Testing this system in Experimental Autoimmune Encephalomyelitis (EAE), animal model of MS, we found that spinal cord B cell depletion ameliorates the disease course and pathology.