Novel autologous dendritic cell vaccine therapy targeting HTLV-1 specific antigen Combined with anti-CCR4 antibody for previously treated patients with adult T-cell leukemia. A phase Ia/Ib study. - Phase Ia/Ib study of Tax-targeting DC vaccine combined with anti-CCR4 Ab for ATL

开始日期2015-03-13

申办/合作机构

Japan Agency for Medical Research & Development

100 项与 Tax peptide-pulsed dendritic cell vaccine(Tokyo Medical & Dental University) 相关的临床结果

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100 项与 Tax peptide-pulsed dendritic cell vaccine(Tokyo Medical & Dental University) 相关的转化医学

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100 项与 Tax peptide-pulsed dendritic cell vaccine(Tokyo Medical & Dental University) 相关的专利（医药）

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项与 Tax peptide-pulsed dendritic cell vaccine(Tokyo Medical & Dental University) 相关的文献（医药）

2019-12-01·Retrovirology2区 · 医学

Impact of host immunity on HTLV-1 pathogenesis: potential of Tax-targeted immunotherapy against ATL

2区 · 医学

ReviewOA

作者: Kimpara, Shuichi ; Hasegawa, Atsuhiko ; Kannagi, Mari ; Nagano, Yoshiko ; Suehiro, Youko

Human T-cell leukemia virus type-1 (HTLV-1) causes adult T-cell leukemia/lymphoma (ATL), HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP), and other inflammatory diseases. There is no disease-specific difference in viral strains, and it is unclear how HTLV-1 causes such different diseases manifesting as lymphoproliferation or inflammation. Although some progress has been made in therapies for these diseases, the prognosis for ATL is still dismal and HAM/TSP remains an intractable disease. So far, two regulatory proteins of HTLV-1, Tax and HBZ, have been well studied and shown to have pleiotropic functions implicated in viral pathogenesis. Tax in particular can strongly activate NFκB, which is constitutively activated in HTLV-1-infected cells and considered to contribute to both oncogenesis and inflammation. However, the expression level of Tax is very low in vivo, leading to confusion in understanding its role in viral pathogenesis. A series of studies using IL-2-dependent HTLV-1-infected cells indicated that IL-10, an anti-inflammatory/immune suppressive cytokine, could induce a proliferative phenotype in HTLV-1-infected cells. In addition, type I interferon (IFN) suppresses HTLV-1 expression in a reversible manner. These findings suggest involvement of host innate immunity in the switch between lymphoproliferative and inflammatory diseases as well as the regulation of HTLV-1 expression. Innate immune responses also affect another important host determinant, Tax-specific cytotoxic T lymphocytes (CTLs), which are impaired in ATL patients, while activated in HAM/TSP patients. Activation of Tax-specific CTLs in ATL patients after hematopoietic stem cell transplantation indicates Tax expression and its fluctuation in vivo. A recently developed anti-ATL therapeutic vaccine, consisting of Tax peptide-pulsed dendritic cells, induced Tax-specific CTL responses in ATL patients and exhibited favorable clinical outcomes, unless Tax-defective ATL clones emerged. These findings support the significance of Tax in HTLV-1 pathogenesis, at least in part, and encourage Tax-targeted immunotherapy in ATL. Host innate and acquired immune responses induce host microenvironments that modify HTLV-1-encoded pathogenesis and establish a complicated network for development of diseases in HTLV-1 infection. Both host and viral factors should be taken into consideration in development of therapeutic and prophylactic strategies in HTLV-1 infection.

2017-01-01·[Rinsho ketsueki] The Japanese journal of clinical hematology

Molecular pathogenesis and its therapeutic implication for ATL.

Article

作者: Ishitsuka, Kenji

Adult T-cell leukemia/lymphoma (ATL) is a peripheral T-cell malignancy caused by human T-lymphotropic virus type I (HTLV-1). HTLV-1 related proteins Tax and HTLV-1 bZIP factor induce immortalization and transformation of HTLV-1-infected T-lymphocytes and eventually induce clonal proliferation. One of the apparent molecular features in ATL cells is abundant genomic abnormalities targeting characteristic pathways, including T-cell receptor signaling and the NF-κB pathway, G-protein coupled-receptor, including CCR4, and transcriptional regulation. Moreover, the overexpression of PD-L1 caused by structural variations in the 3'-UTR of the PD-L1 gene has been reported recently, which indicates possible escape of ATL cells from immune-surveillance and its therapeutic application for pharmacological intervention. The next is the downregulation of microRNAs and tumor suppressors by genome-wide epigenetic abnormalities, especially accumulation of trimethylated H3K27 induced by EZH2. Among these molecular events frequently observed in ATL cells, treatment targeting CCR4 via a monoclonal antibody has been introduced in the clinic, and immune-therapy by therapeutic vaccine with Tax peptide-pulsed dendritic cells, treatment by immune checkpoint inhibitors, and treatment targeting EZH1/2 by a small molecule inhibitor are under clinical trial. Establishment of novel treatment strategies beyond cytotoxic agents for ATL are eagerly anticipated, especially for elderly patients.

2015-05-01·British Journal of Haematology2区 · 医学

Clinical outcomes of a novel therapeutic vaccine with Tax peptide‐pulsed dendritic cells for adult T cell leukaemia/lymphoma in a pilot study

2区 · 医学

Article

作者: Fukuda, Tetsuya ; Miura, Osamu ; Sasada, Amane ; Watanabe, Nobukazu ; Akashi, Koichi ; Choi, Ilseung ; Matsuoka, Masao ; Tanosaki, Ryuji ; Suehiro, Youko ; Kannagi, Mari ; Hasegawa, Atsuhiko ; Takamori, Ayako ; Utsunomiya, Atae ; Iino, Tadafumi ; Teshima, Takanori ; Uike, Naokuni ; Okamura, Jun ; Takaishi, Shigeo

SummaryAdult T cell leukaemia/lymphoma (ATL) is a human T cell leukaemia virus type‐I (HTLV‐I)‐infected T cell malignancy with poor prognosis. We herein developed a novel therapeutic vaccine designed to augment an HTLV‐I Tax‐specific cytotoxic T lymphocyte (CTL) response that has been implicated in anti‐ATL effects, and conducted a pilot study to investigate its safety and efficacy. Three previously treated ATL patients, classified as intermediate‐ to high‐risk, were subcutaneously administered with the vaccine, consisting of autologous dendritic cells (DCs) pulsed with Tax peptides corresponding to the CTL epitopes. In all patients, the performance status improved after vaccination without severe adverse events, and Tax‐specific CTL responses were observed with peaks at 16–20 weeks. Two patients achieved partial remission in the first 8 weeks, one of whom later achieved complete remission, maintaining their remission status without any additional chemotherapy 24 and 19 months after vaccination, respectively. The third patient, whose tumour cells lacked the ability to express Tax at biopsy, obtained stable disease in the first 8 weeks and later developed slowly progressive disease although additional therapy was not required for 14 months. The clinical outcomes of this pilot study indicate that the Tax peptide‐pulsed DC vaccine is a safe and promising immunotherapy for ATL.

100 项与 Tax peptide-pulsed dendritic cell vaccine(Tokyo Medical & Dental University) 相关的药物交易

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研发状态

10 条进展最快的记录,

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适应症	最高研发状态	国家/地区	公司	日期
T细胞淋巴瘤	临床1期	-	Tokyo Medical & Dental University	-
T细胞淋巴瘤	临床1期	-	Kumamoto University	-
T细胞淋巴瘤	临床1期	-	Kyoto University	-
T细胞淋巴瘤	临床1期	-	Tottori University	-
T细胞淋巴瘤	临床1期	-	Kyushu University	-