HTLV–1関連脊髄症に対するヒト化抗CCR4抗体療法開発の背景

抄録

Some infected with human T–lymphotropic virus type 1 (HTLV–1), which causes adult T cell leukemia/lymphoma (ATL), develop the neurodegenerative disease HTLV–1 associated myelopathy (HAM). Suffering from progressive spinal cord paralysis, HAM patients experience a low quality of life with high unmet needs. Thus, the prognosis for HAM patients is extremely poor, and there is a strong demand for a novel therapeutic strategy. We established a HAM national patient registration system (HAM–net) in collaboration with patient groups to gather data from and distribute information to patients on a nation–wide scale. Recently we showed that HTLV–1 mainly infects CCR4^＋ T–cells and causes functional abnormalities that are believed to drive HAM pathogenesis. We next demonstrated that anti–CCR4 antibody treatments could target infected cells of HAM patients. Finally, we began an Investigator–led clinical trial. Despite patients scattered few and far between across the nation, securing participants is going well thanks to the HAM–net registration system. This Phase I/IIa trial involves 21 HAM patients undergoing steroid maintenance therapy. With safety as the primary endpoint, we investigate the maximum tolerated dose and pharmacokinetics ; secondary endpoints include walking times and activity against infected cells. This trial is the first to evaluate a drug targeting infected cells in HAM patients, and we anticipate an imminent change in the HAM treatment paradigm. (UMIN000012655)