Health-related quality of life in Japanese patients with multiple sclerosis.

OBJECTIVES: Neurological disabilities, especially physical issues, can adversely affect the daily lives of people with multiple sclerosis (MS) and negatively impact their health-related quality of life (HRQOL). On the other hand, physical and psychiatric symptoms are variable in people with MS, and QOL can be influenced by cultural and educational background. This study aimed to evaluate the association of HRQOL with disabilities, fatigue, and depression in Japanese subjects with MS. METHODS: Evaluation of HRQOL, fatigue, and depression was performed in 184 Japanese individuals with MS, using the Functional Assessment of MS (FAMS), Fatigue Severity Scale (FSS), and Beck Depression Inventory-Second Edition (BDI-II), respectively. RESULTS: Multiple linear regression analysis demonstrated negative correlations of the Expanded Disability Status Scale (EDSS) with scores on the FAMS subscales of mobility, symptoms, thinking and fatigue, total FAMS, and additional concerns. The FSS score had negative correlations with mobility, symptoms, emotional well-being, thinking and fatigue, total FAMS, and additional concerns. There were negative correlations between BDI-II scores and all items of FAMS. CONCLUSIONS: HRQOL had relatively close correlations with disabilities and fatigue, and depression had an especially close relationship with HRQOL.

Effect of wine pomace extract on dechlorination of chloroethenes in soil suspension.

Chloroethenes are widely used as solvent in the metal industry and the dry cleaning industry, but their spillage into soil and groundwater due to improper handling has negatively impacted human health. Bioremediation using microorganisms is one of the technologies to clean up soil and groundwater contaminated with chloroethenes. In this study, we examined the bioremediation of chloroethene-contaminated soil using wine pomace extract (WPE). WPE is a liquid containing seven major carboxylic acids and other substances extracted from grape pomace produced in winemaking. WPE clearly promoted the anaerobic bioremediation of chloroethenes. In the tetrachloroethene (PCE) degradation test that used fractions derived from WPE, the water-eluted fraction containing L-lactic acid, L-tartaric acid, and others promoted the dechlorination of PCE, whereas the methanol-eluted fraction containing mainly syringic acid did not. In another PCE degradation test that used L-lactic acid, L-tartaric acid, and syringic acid test solutions, L-lactic acid and L-tartaric acid enhanced the dechlorination of PCE, but syringic acid did not. The results suggest that L-lactic acid and L-tartaric acid in WPE function as hydrogen donors in the anaerobic microbial degradation of chloroethene. This technology realizes environmental remediation through the effective use of food by-products.

Remote ischemic conditioning for acute ischemic stroke part 2: Study protocol for a randomized controlled trial.

Background: Remote ischemic conditioning (RIC) refers to the application of repeated short periods of ischemia intended to protect remote areas against tissue damage during and after prolonged ischemia. Aim: We aim to evaluate the efficacy of RIC, determined by the modified Rankin Scale (mRS) score at 90 days after stroke onset. Design and methods: This study is an investigator-initiated, multicenter, prospective, randomized, open-label, parallel-group clinical trial. The sample size is 400, comprising 200 patients who will receive RIC and 200 controls. The patients will be divided into three groups according to their National Institutes of Health Stroke Scale score at enrollment: 5-9, mild; 10-14, moderate; 15-20, severe. The RIC protocol will be comprised of four cycles, each consisting of 5 min of blood pressure cuff inflation (at 200 mmHg or 50 mmHg above the systolic blood pressure) followed by 5 min of reperfusion, with the cuff placed on the thigh on the unaffected side. The control group will only undergo blood pressure measurements before and after the intervention period. This trial is registered with the UMIN Clinical Trial Registry (https://www.umin.ac.jp/: UMIN000046225). Study outcome: The primary outcome will be a good functional outcome as determined by the mRS score at 90 days after stroke onset, with a target mRS score of 0-1 in the mild group, 0-2 in the moderate group, and 0-3 in the severe group. Discussion: This trial may help determine whether RIC should be recommended as a routine clinical strategy for patients with ischemic stroke.

[Disability Progression in SPMS Despite Therapeutic Intervention: Current Status and Perspectives of Treatment with Disease-Modifying Drugs].

Currently, siponimod is the only disease-modifying drugs (DMDs) with proven efficacy and safety in clinical trials for secondary progressive multiple sclerosis (SPMS). However, the efficacy of siponimod in preventing disability progression is insufficient and it has not yet been able to deter disability progression. Therefore, it is considered necessary to use DMDs with a high relapse-preventive effect at a relatively early stage of SPMS, while disease activity remains evident. Bruton's tyrosine kinase inhibitors have the potential to prevent progression of all MS disease types and are expected to be the cornerstone of the next generation of treatment. The results of these clinical trials are awaited.

Clinical Efficacy and Safety of Arbekacin against Pneumonia in Febrile Neutropenia: A Retrospective Study in Patients with Hematologic Malignancies.

BACKGROUND: Arbekacin (ABK) is an aminoglycoside that exhibits anti-methicillin-resistant Staphylococcus aureus (MRSA) and anti-Pseudomonas aeruginosa activities. Therefore, for patients with febrile neutropenia (FN) and concurrent pneumonia suspected to be caused by MRSA, ABK may be sufficiently effective even as a single agent. MATERIALS AND METHODS: Patients with hematologic malignancies treated with ABK who met the following criteria were included: 1) fever during neutropenia or functional neutropenia, 2) FN complicated by pneumonia, and 3) possible infection by antimicrobial-resistant Gram-positive cocci. RESULTS: This study encompassed 22 episodes involving 19 patients, of which, 15 (68.2%) were successfully treated with ABK. Of the nine episodes showing inadequate response to other anti-MRSA drugs, eight were successfully treated with ABK. Grade 2 or worse adverse events included acute kidney injury (13.6%) and increased transaminase levels (9.1%). CONCLUSION: The present study demonstrated that ABK is effective and safe in patients with FN and concurrent pneumonia caused by antimicrobial-resistant Gram-positive cocci. ABK may also be effective in patients who are unresponsive to other anti-MRSA drugs. Therefore, ABK may be beneficial in the treatment of pneumonia caused by antimicrobial-resistant Gram-positive cocci in patients with FN.

Correlation of the symbol digit modalities test with the quality of life and depression in Japanese patients with multiple sclerosis.

BACKGROUND: This study aimed to evaluate the association between cognitive impairment and health-related quality of life (HRQOL), fatigue, and depression in Japanese patients with multiple sclerosis (MS). METHODS: The Brief International Cognitive Assessment for MS (BICAMS) was performed in 184 Japanese patients with MS. The Functional Assessment of MS (FAMS), Fatigue Severity Scale (FSS), and Beck Depression Inventory-Second Edition (BDI-II) were used to evaluate HRQOL, fatigue, and depression, respectively. RESULTS: Multiple linear regression analysis demonstrated positive correlations of the Symbol Digit Modalities Test (SDMT) with the scores on the FAMS subscales of mobility, symptoms, emotional well-being, and additional concerns and with the total FAMS score even after controlling for the Expanded Disability Status Scale score, age at examination, and duration of education. The SDMT score in the BICAMS battery had negative correlations with the BDI-II score, as revealed by multiple linear regression analysis. None of the three tests in the BICAMS had any correlation with the FSS score. CONCLUSION: The SDMT has a significant relationship with HRQOL and depression in Japanese patients with MS.

HLA genotype-clinical phenotype correlations in multiple sclerosis and neuromyelitis optica spectrum disorders based on Japan MS/NMOSD Biobank data.

HLA genotype-clinical phenotype correlations are not established for multiple sclerosis (MS) and neuromyelitis optica spectrum disorders (NMOSD). We studied HLA-DRB1/DPB1 genotype-phenotype correlations in 528 MS and 165 NMOSD cases using Japan MS/NMOSD Biobank materials. HLA-DRB1*04:05, DRB1*15:01 and DPB1*03:01 correlated with MS susceptibility and DRB1*01:01, DRB1*09:01, DRB1*13:02 and DPB1*04:01 were protective against MS. HLA-DRB1*15:01 was associated with increased optic neuritis and cerebellar involvement and worsened visual and pyramidal functional scale (FS) scores, resulting in higher progression index values. HLA-DRB1*04:05 was associated with younger onset age, high visual FS scores, and a high tendency to develop optic neuritis. HLA-DPB1*03:01 increased brainstem and cerebellar FS scores. By contrast, HLA-DRB1*01:01 decreased spinal cord involvement and sensory FS scores, HLA-DRB1*09:01 decreased annualized relapse rate, brainstem involvement and bowel and bladder FS scores, and HLA-DRB1*13:02 decreased spinal cord and brainstem involvement. In NMOSD, HLA-DRB1*08:02 and DPB1*05:01 were associated with susceptibility and DRB1*09:01 was protective. Multivariable analysis revealed old onset age, long disease duration, and many relapses as independent disability risks in both MS and NMOSD, and HLA-DRB1*15:01 as an independent risk only in MS. Therefore, both susceptibility and protective alleles can influence the clinical manifestations in MS, while such genotype-phenotype correlations are unclear in NMOSD.

Efficacy and safety of dimethyl fumarate in treatment-naïve Japanese patients with multiple sclerosis: Interim analysis of the randomized placebo-controlled study.

BACKGROUND: The use of dimethyl fumarate has not been reported in treatment-naïve Japanese patients with relapsing-remitting multiple sclerosis. OBJECTIVES: The purpose of this study was to evaluate the efficacy and safety of dimethyl fumarate in treatment-naïve Japanese patients with relapsing-remitting multiple sclerosis. METHODS: APEX was a phase 3, multinational trial, which consisted of a 24-week, randomized (1:1), double-blind study where patients received dimethyl fumarate 240 mg or placebo twice daily, followed by an open-label extension where all patients received dimethyl fumarate 240 mg. The primary endpoints were the total number of new gadolinium-enhancing (Gd+) lesions in Weeks 12-24 (Part I) and long-term safety (Part II). This post-hoc subgroup analysis evaluated the efficacy and safety of dimethyl fumarate in treatment-naïve Japanese patients with relapsing-remitting multiple sclerosis (n=52) up to Week 72 (24 weeks Part I and 48 weeks Part II). RESULTS: Dimethyl fumarate reduced the mean total number of new gadolinium-enhancing lesions at Weeks 12-24 by 94% versus placebo; the number of patients who had a relapse over 24 weeks was reduced by 72%. Adverse events leading to discontinuation of the study drug were reported in 9% of patients receiving placebo/dimethyl fumarate and 4% of patients in dimethyl fumarate/dimethyl fumarate. CONCLUSIONS: Dimethyl fumarate demonstrated sustained efficacy and acceptable tolerability in treatment-naïve Japanese patients with relapsing-remitting multiple sclerosis for 72 weeks.

A case of cerebral tuberculoma mimicking neurocysticercosis.

Case: A 42-year-old Peruvian woman residing in Japan for 11 years with a family history of neurocysticercosis presented to our intensive care unit with fever and intense headache.Computed tomography indicated multiple micronodular lesions in the brain parenchyma, and cerebral tuberculoma and neurocysticercosis were considered in the differential diagnosis. Neurocysticercosis was initially suspected, and oral praziquantel was initiated. However, because of a high adenosine deaminase level in the cerebrospinal fluid and positive peripheral blood interferon gamma release test result, cerebral tuberculoma was subsequently considered. Outcome: Antituberculous drugs with steroids were initiated on day 10, after which the symptoms gradually resolved; the patient was discharged on day 29. Gadolinium-contrast magnetic resonance imaging 8 months later showed reduced nodular shadows, confirming cerebral tuberculoma. Conclusion: Immediate diagnosis and treatment are imperative for cerebral tuberculoma, a lethal infection. Considering the recent increases in immigration worldwide, increased cases of tuberculoma mimicking neurocysticercosis are expected.

[A case of anti-MOG antibody-positive multiphasic disseminated encephalomyelitis co-occurring with unilateral cerebral cortical encephalitis].

A 20-year-old woman first developed acute disseminated encephalomyelitis (ADEM) at 11 years of age. At 17 years of age, she was hospitalized due to generalized seizure and diagnosed with encephalitis. Brain MRI revealed a FLAIR-hyperintense lesion in the unilateral cerebral cortex. At 18 years of age, serum anti-myelin oligodendrocyte glycoprotein (MOG) antibody was detected. At 20 years of age, she was admitted to our hospital, diagnosed with multifocal disseminated encephalomyelitis (MDEM). MDEM has been observed in patients that are seropositive for the anti-MOG antibody. More recently, unilateral cerebral cortex encephalitis with epilepsy has also been reported in such patients. The co-occurrence of MDEM and cortical encephalitis in the same patient has important implications for the pathogenesis of anti-MOG antibody-associated autoimmune diseases.

Nik-related kinase regulates trophoblast proliferation and placental development by modulating AKT phosphorylation.

Nik-related kinase (Nrk) is a Ser/Thr kinase and was initially discovered as a molecule that was predominantly detected in skeletal muscles during development. A recent study using Nrk-null mice suggested the importance of Nrk in proper placental development; however, the molecular mechanism remains unknown. In this study, we demonstrated that differentiated trophoblasts from murine embryonic stem cells (ESCs) endogenously expressed Nrk and that Nrk disruption led to the enhanced proliferation of differentiated trophoblasts. This phenomenon may reflect the overproliferation of trophoblasts that has been reported in enlarged placentas of Nrk-null mice. Furthermore, we demonstrated that AKT phosphorylation at Ser473 was upregulated in Nrk-null trophoblasts and that inhibition of AKT phosphorylation cancelled the enhanced proliferation observed in differentiated Nrk-null trophoblasts. These results indicated that the upregulation of AKT phosphorylation was the possible cause of enhanced proliferation observed in Nrk-null trophoblasts. The upregulation of AKT phosphorylation was also confirmed in enlarged Nrk-null placentas in vivo, suggesting that proper regulation of AKT by Nrk was important for normal placental development. In addition, our detailed analysis on phosphorylation status of AKT isoforms in newly established trophoblast stem cells (TSCs) revealed that different levels of upregulation of AKT phosphorylation were occurred in Nrk-null TSCs depending on AKT isoforms. These results further support the importance of Nrk in proper development of trophoblast lineage cells and indicate the possible application of TSCs for the analysis of differently regulated activation mechanisms of AKT isoforms.

Validation of the Brief International Cognitive Assessment for Multiple Sclerosis in Japan.

BACKGROUND: The Brief International Cognitive Assessment for MS (BICAMS) is a practical battery for measuring cognitive function in multiple sclerosis (MS). OBJECTIVES: We aimed to validate a Japanese version of the BICAMS in patients with MS and healthy controls. METHODS: The Symbol Digit Modalities Test (SDMT), the California Verbal Learning Test-Second Edition (CVLT2) and the Brief Visuospatial Memory Test Revised (BVMTR) were administered to 156 patients with MS and 126 healthy controls (HCs). The BICAMS was re-administered in a subset of 27 MS patients and 30 HCs. RESULTS: The mean (±SD) raw scores in the MS and HC groups were as follows: SDMT: MS 47.9 ± 14.0, HC 61.0 ± 9.5; CVLT2: MS 48.6 ± 12.6, HC 55.7 ± 10.5; BVMTR: MS 23.5 ± 8.4, HC 28.3 ± 5.4, respectively, and significant differences were found between the two groups on all tests (p < 0.0001). Cohen's d values were 1.07, 0.60, and 0.67 in SDMT, CVLT2, and BVMTR, respectively. The test-retest reliability coefficients for each test were as follows: SDMT: r = 0.93; CVLT2: r = 0.82; and BVMTR: r = 0.77 (p < 0.0001). CONCLUSIONS: This study provides results that support the reliability and validity of the BICAMS in Japan.

A case of posterior reversible leukoencephalopathy syndrome caused by fibromuscular dysplasia.

A 23-year-old woman presented with disturbance of consciousness and seizure. Her blood pressure was remarkably high, and brain magnetic resonance imaging (MRI) showed high-intensity T2 signals in the bilateral basal ganglia, corpus callosum, cerebral white matter, and cortex. With the administration of angiotensin II receptor blocker, the symptoms and MRI findings improved, along with normalization of blood pressure, and a diagnosis of posterior reversible leukoencephalopathy syndrome (PRES) was made. Plasma renin activity was high, and the right kidney was severely atrophic. Results from renal and adrenal vein sampling revealed renal vascular hypertension derived from the right renal artery stenosis. The right kidney was then removed by laparoscopic nephrectomy. Pathological examination of the kidney confirmed the diagnosis of fibromuscular dysplasia (FMD). In juvenile-onset encephalitis/encephalopathy, PRES due to FMD should be included in the differential diagnosis.

Efficacy of intravenous methylprednisolone pulse therapy in patients with multiple sclerosis and neuromyelitis optica.

BACKGROUND: No large-scale studies have compared the efficacy of intravenous methylprednisolone pulse therapy (IVMP) for multiple sclerosis (MS) and neuromyelitis optica (NMO). OBJECTIVE: To explain differences in treatment responses of MS and NMO patients to IVMP. METHODS: Changes in neurological symptoms/signs and Expanded Disability Status Scale (EDSS) scores before and within 1 week of IVMP completion were obtained in 2010 at 28 institutions, and retrospectively collated from 271 MS (478 courses) and 73 NMO (118 courses) cases. RESULTS: In MS patients, decreased EDSS score was significant after the first (-0.8 ± 0.9), second (-0.7 ± 0.9), and third (-0.7 ± 0.8) courses (p < 0.05), but not after the fourth (-0.3 ± 0.7) and fifth (-0.5 ± 0.6). However, decreased EDSS score was only significant after the first course (-0.5 ± 1.5, p < 0.05) in NMO patients. EDSS score was significantly decreased in MS compared with NMO patients at the first course (p < 0.05), but not thereafter. Model analysis for EDSS score improvement at the first course, adjusting for covariates, showed significantly greater decreases in MS compared with NMO patients (p < 0.05). CONCLUSION: IVMP is effective in MS from the first to third courses, and in NMO at the first course. Additionally, IVMP is more efficacious in MS than NMO patients, even at the first course.

Pregnancy-related relapse risk factors in women with anti-AQP4 antibody positivity and neuromyelitis optica spectrum disorder.

BACKGROUND: Few reports describe the influence pregnancy has on the annualized relapse rate (ARR) in neuromyelitis optica spectrum disorder (NMOSD). OBJECTIVE: To examine pregnancy-related attacks (attacks during pregnancy or within 1 year postpartum) and identify the risk factors for an attack in Japanese NMOSD patients. METHODS: We retrospectively reviewed 139 Japanese women whom had aquaporin-4 (AQP4) antibody-positive NMOSD. Among the 114 patients with information, 47 women had 56 pregnancies. We compared the ARR before, during and after pregnancy. RESULTS: Of the 47 NMOSD patients with pregnancy, 22 women (46.8%) had a pregnancy-related attack of the disease (either an onset event or a relapse). The ARR was significantly higher in the first 3 months postpartum (1.80 ± 2.04), than before the pregnancy (0.57 ± 1.16; p = 0.0043) and did not significantly decrease during pregnancy. The ARR before hospitalization and treatment was analyzable in 55 patients without pregnancy and was 1.09 ± 1.17. Among the 11 patients with onset before pregnancy, nine patients had a pregnancy-related attack with a relapse in the previous year, and their immunosuppression was discontinued or made to be at low doses; while the two patients on higher-dose therapies were relapse-free. CONCLUSION: In the present study, pregnancy-related attack was common in NMOSD, and unlike in multiple sclerosis, the ARR was not reduced during pregnancy. Discontinued or insufficient immunosuppression appeared to increase the risk of pregnancy-related attack.

Osteopontin-integrin interaction as a novel molecular target for antibody-mediated immunotherapy in adult T-cell leukemia.

BACKGROUND: Adult T-cell leukemia (ATL) is a CD4(+) T-cell neoplasm with a poor prognosis. A previous study has shown that there is a strong correlation between the secreted matricellular protein osteopontin (OPN) level and disease severity in ATL patients. Here, we investigated the role of OPN in ATL pathogenesis and the possible application of anti-OPN monoclonal antibody (mAb) for ATL immunotherapy in NOD/Shi-scid,IL-2Rg (null) (NOG) mice. RESULTS: Subcutaneous inoculation of ATL cell lines into NOG mice increased the plasma level of OPN, which significantly correlated with metastasis of the inoculated cells and survival time. Administration of an SVVYGLR motif-recognizing anti-OPN mAb resulted in inhibition not only of tumor growth but also of tumor invasion and metastasis. The number of fibroblast activating protein-positive fibroblasts was also reduced by this mAb. We then co-inoculated mouse embryonic fibroblasts (MEFs) isolated from wild-type (WT) or OPN knockout mice together with ATL-derived TL-OmI cells into the NOG mice. The mice co-inoculated with WT MEFs displayed a significant decrease in survival relative to those injected with TL-OmI cells alone and the absence of OPN in MEFs markedly improved the survival rate of TL-OmI-inoculated mice. In addition, tumor volume and metastasis were also reduced in the absence of OPN. CONCLUSION: We showed that the xenograft NOG mice model can be a useful system for assessment of the physiological role of OPN in ATL pathogenesis. Using this xenograft model, we found that fibroblast-derived OPN was involved in tumor growth and metastasis, and that this tumor growth and metastasis was significantly suppressed by administration of the anti-OPN mAbs. Our findings will lead to a novel mAb-mediated immunotherapeutic strategy targeting against the interaction of OPN with integrins on the tumor of ATL patients.

TDP-43 Pathology Progression Along the Olfactory Pathway as a Possible Substrate for Olfactory Impairment in Amyotrophic Lateral Sclerosis.

Odor impairment and its relationship with TAR DNA-binding protein 43 (TDP-43) pathology in patients with amyotrophic lateral sclerosis (ALS) have not been fully elucidated. We performed the odor stick identification test for Japanese (OSIT-J) in 18 ALS patients and in 18 controls. The score was significantly decreased (6.6 ± 2.7) in the patients versus the controls (9.2 ± 2.4) (U = 77.0, p = 0.007). This decrement of the OSIT-J score paralleled the cognitive decline. We then studied samples from a series of 42 postmortem ALS cases. Quantitative analyses demonstrated that TDP-43-positive inclusions were most frequent in the hippocampus and least abundant in the olfactory bulb and were of intermediate density in the primary olfactory cortex. This centrifugal gradient suggests that TDP-43 pathology starts in the hippocampus, spreads into the primary olfactory center, and finally reaches the olfactory bulb. TDP-43, tau, and α-synuclein accumulations appeared to be independent. These observations suggest that impaired odor discrimination in ALS patients may be related to TDP-43-positive lesions affecting predominantly secondary olfactory centers (especially the hippocampus) in contrast to decreased odor sensitivity in Parkinson disease in which α-synuclein pathology mainly involves the peripheral region (i.e., olfactory bulb). We suggest that detectable odor impairments in ALS patients are useful for predicting the presence of TDP-43 pathology in the extramotor system.

[Short-term high-dose intravenous methylprednisolone therapy].

Short-term, high-dose intravenous methylprednisolone therapy (IVMP), which is called steroid pulse therapy, is widely used as the standard treatment for acute exacerbations of multiple sclerosis (MS), and has been shown to improve neurological symptoms. IVMP is also applied in the acute phase of neuromyelitis optica (NMO), with considerable benefit, although some patients are refractory to IVMP, and the early use of plasmapheresis should be considered in these patients. IVMP acts by inhibiting the cascade of inflammation through several different mechanisms, including reducing the inflammatory cytokines and suppressing the T cell activation. IVMP is well tolerated and relatively safe, but attention should be paid to the development of adverse events, such as psychosis, hyperglycemia and osteonecrosis.

Combined cytolytic effects of a vaccinia virus encoding a single chain trimer of MHC-I with a Tax-epitope and Tax-specific CTLs on HTLV-I-infected cells in a rat model.

Adult T cell leukemia (ATL) is a malignant lymphoproliferative disease caused by human T cell leukemia virus type I (HTLV-I). To develop an effective therapy against the disease, we have examined the oncolytic ability of an attenuated vaccinia virus (VV), LC16m8Δ (m8Δ), and an HTLV-I Tax-specific cytotoxic T lymphocyte (CTL) line, 4O1/C8, against an HTLV-I-infected rat T cell line, FPM1. Our results demonstrated that m8Δ was able to replicate in and lyse tumorigenic FPM1 cells but was incompetent to injure 4O1/C8 cells, suggesting the preferential cytolytic activity toward tumor cells. To further enhance the cytolysis of HTLV-I-infected cells, we modified m8Δ and obtained m8Δ/RT1AlSCTax180L, which can express a single chain trimer (SCT) of rat major histocompatibility complex class I with a Tax-epitope. Combined treatment with m8Δ/RT1AlSCTax180L and 4O1/C8 increased the cytolysis of FPM1V.EFGFP/8R cells, a CTL-resistant subclone of FPM1, compared with that using 4O1/C8 and m8Δ presenting an unrelated peptide, suggesting that the activation of 4O1/C8 by m8Δ/RT1AlSCTax180L further enhanced the killing of the tumorigenic HTLV-I-infected cells. Our results indicate that combined therapy of oncolytic VVs with SCTs and HTLV-I-specific CTLs may be effective for eradication of HTLV-I-infected cells, which evade from CTL lysis and potentially develop ATL.