Bogie Jeroen Fj, Grajchen Elien, Wouters Elien, Broux Bieke, Stinissen Piet, Van Wijmeersch Bart, Hendriks Jerome Ja
Department of Immunology and Infection, Biomedical Research Institute, Hasselt University, Diepenbeek, Belgium.
Department of Immunology and Infection, Biomedical Research Institute, Hasselt University, Agoralaan Building C, Diepenbeek, 3590, Belgium.
Ther Adv Chronic Dis. 2020 Aug 21;11:2040622320947378. doi: 10.1177/2040622320947378. eCollection 2020.
Alemtuzumab is a humanized monoclonal antibody that depletes CD52-bearing B and T lymphocytes. Clinical trials defined that systemic administration of alemtuzumab reduces disease severity in the relapsing-remitting phase of multiple sclerosis (MS). However, its efficacy in progressive MS patients is limited, which may reflect the inability of alemtuzumab to cross the reconstituted BBB in these patients. Objective: to study whether central nervous system (CNS) delivery of anti-CD52 antibodies reduces disease severity and the neuroinflammatory burden in the experimental autoimmune encephalomyelitis (EAE) model.
Anti-CD52 antibodies were administered intrathecally during the acute and chronic phases of EAE. Flow cytometry and immunohistochemistry were utilized to define immunological and pathological parameters.
We show that subcutaneously administrated anti-CD52 antibodies completely abolish EAE disease severity. CNS delivery of anti-CD52 antibodies during both the acute and chronic phases of EAE moderately reduces disease severity and the neuroinflammatory burden. Our findings further suggest that CNS delivery of anti-CD52 antibodies impacts both the peripheral and CNS immune cell compartments in the EAE model but not in healthy mice.
Collectively, our findings highlight the therapeutic potential of CNS delivery of alemtuzumab for the treatment of progressive as well as early MS.
阿仑单抗是一种人源化单克隆抗体，可清除表达CD52的B淋巴细胞和T淋巴细胞。临床试验表明，全身应用阿仑单抗可降低复发缓解型多发性硬化症（MS）的疾病严重程度。然而，其对进展型MS患者的疗效有限，这可能反映出阿仑单抗无法穿过这些患者重建的血脑屏障。目的：研究在实验性自身免疫性脑脊髓炎（EAE）模型中，中枢神经系统（CNS）递送抗CD52抗体是否能降低疾病严重程度和神经炎症负担。
在EAE的急性期和慢性期鞘内注射抗CD52抗体。利用流式细胞术和免疫组织化学来确定免疫和病理参数。
我们发现皮下注射抗CD52抗体可完全消除EAE的疾病严重程度。在EAE的急性期和慢性期，CNS递送抗CD52抗体可适度降低疾病严重程度和神经炎症负担。我们的研究结果进一步表明，在EAE模型中，而非健康小鼠中，CNS递送抗CD52抗体对外周和CNS免疫细胞区室均有影响。
总的来说，我们的研究结果突出了CNS递送阿仑单抗治疗进展型和早期MS的治疗潜力。
