From the Departments of Stem Cell Transplantation and Cellular Therapy (M.M., A.O., D.M., S.A., I.K., L.L., R.C., E.J.S., K.R.), Infectious Diseases (V.M.), Neuro-Oncology (S.T.), Diagnostic Radiology (T.L.C.), and Leukemia (A.F.), M.D. Anderson Cancer Center, Houston.
N Engl J Med. 2018 Oct 11;379(15):1443-1451. doi: 10.1056/NEJMoa1801540.
JC virus, the cause of progressive multifocal leukoencephalopathy (PML), and the BK virus are genetically similar and share sequence homology in immunogenic proteins. We treated three immunosuppressed patients with PML with ex vivo-expanded, partially HLA-matched, third-party-produced, cryopreserved BK virus-specific T cells. The immunosuppression in these patients was due to the conditioning regimen for cord-blood transplantation in one patient, a myeloproliferative neoplasm treated with ruxolitinib in another, and acquired immunodeficiency syndrome in the third. After T-cell infusion in two of the patients, alleviation of the clinical signs and imaging features of PML was seen and JC virus in the cerebrospinal fluid (CSF) cleared. The other patient had a reduction in JC viral load and stabilization of symptoms that persisted until her death 8 months after the first infusion. Two of the patients had immune reconstitution syndrome. Donor-derived T cells were detected in the CSF after infusion. (Funded by the M.D. Anderson Cancer Center Moon Shots Program and the National Institutes of Health; ClinicalTrials.gov number, NCT02479698 .).
JC 病毒是进行性多灶性白质脑病(PML)的病因,与 BK 病毒在遗传上相似,并在免疫原性蛋白中具有序列同源性。我们用体外扩增的、部分 HLA 匹配的、第三方生产的、冷冻保存的 BK 病毒特异性 T 细胞治疗了 3 例 PML 免疫抑制患者。这些患者的免疫抑制是由于一名患者接受了脐带血移植的预处理方案,另一名患者接受了鲁索利替尼治疗骨髓增生性肿瘤,还有一名患者患有获得性免疫缺陷综合征。在两名患者中输注 T 细胞后,PML 的临床症状和影像学特征得到缓解,脑脊液中的 JC 病毒清除。另一名患者的 JC 病毒载量减少,症状稳定,直到第一次输注后 8 个月死亡。两名患者出现免疫重建综合征。输注后在脑脊液中检测到供体来源的 T 细胞。(由 MD 安德森癌症中心 Moon Shots 计划和美国国立卫生研究院资助;临床试验.gov 编号,NCT02479698)。