Potential Contribution of a Novel Tax Epitope–Specific CD4+ T Cells to Graft-versus-Tax Effect in Adult T Cell Leukemia Patients after Allogeneic Hematopoietic Stem Cell Transplantation

Tamai, Yasukatsu; Hasegawa, Atsuhiko; Takamori, Ayako; Sasada, Amane; Tanosaki, Ryuji; Choi, Ilseung; Utsunomiya, Atae; Maeda, Yasuhiro; Yamano, Yoshihisa; Eto, Tetsuya; Koh, Ki Ryang; Nakamae, Hirohisa; Suehiro, Yutaka; Katô, Kôji; Takemoto, Shigeki; Okamura, Jun; Uike, Naokuni; Kannagi, Mari

doi:10.4049/jimmunol.1202971

Cited by 12 publications

(8 citation statements)

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“…On the other hand, the most predominant clinical issue would be to stimulate immune response in HAM/TSP or ATL patients. In this context, an alternative immunotherapy for HTLV-1 would involve vaccination against viral factors, such as Tax and/or HTLV-1 bZIP factor (HBZ), using peptides [43] or expression vectors.…”

Section: A Blv Vaccine As Vector Producing Htlv Neutralizing Antibmentioning

confidence: 99%

Vaccination against δ-Retroviruses: The Bovine Leukemia Virus Paradigm

Gutiérrez

Rodríguez

Brogniez

et al. 2014

Viruses

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Bovine leukemia virus (BLV) and human T-lymphotropic virus type 1 (HTLV-1) are closely related δ-retroviruses that induce hematological diseases. HTLV-1 infects about 15 million people worldwide, mainly in subtropical areas. HTLV-1 induces a wide spectrum of diseases (e.g., HTLV-associated myelopathy/tropical spastic paraparesis) and leukemia/lymphoma (adult T-cell leukemia). Bovine leukemia virus is a major pathogen of cattle, causing important economic losses due to a reduction in production, export limitations and lymphoma-associated death. In the absence of satisfactory treatment for these diseases and besides the prevention of transmission, the best option to reduce the prevalence of δ-retroviruses is vaccination. Here, we provide an overview of the different vaccination strategies in the BLV model and outline key parameters required for vaccine efficacy.

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Section: A Blv Vaccine As Vector Producing Htlv Neutralizing Antibmentioning

confidence: 99%

Vaccination against δ-Retroviruses: The Bovine Leukemia Virus Paradigm

Gutiérrez

Rodríguez

Brogniez

et al. 2014

Viruses

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“…[42][43][44] However, there was no study using Bambanker for cryopreservation of hepatocytes. The current results showed that Bambanker is not suitable for hepatocyte cryopreservation, as it causes some damage to hepatocytes and abnormal cell morphology after thawing.…”

Section: Discussionmentioning

confidence: 99%

Cryopreservation of Hepatocyte Microbeads for Clinical Transplantation

et al. 2017

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Intraperitoneal transplantation of hepatocyte microbeads is an attractive option for the management of acute liver failure. Encapsulation of hepatocytes in alginate microbeads supports their function and prevents immune attack of the cells. Establishment of banked cryopreserved hepatocyte microbeads is important for emergency use. The aim of this study was to develop an optimized protocol for cryopreservation of hepatocyte microbeads for clinical transplantation using modified freezing solutions. Four freezing solutions with potential for clinical application were investigated. Human and rat hepatocytes cryopreserved with University of Wisconsin (UW)/10% dimethyl sulfoxide (DMSO)/5% (300 mM) glucose and CryoStor CS10 showed better postthawing cell viability, attachment, and hepatocyte functions than with histidine-tryptophan-ketoglutarate/10% DMSO/5% glucose and Bambanker. The 2 freezing solutions that gave better results were studied with human and rat hepatocytes microbeads. Similar effects on cryopreserved microbead morphology (external and ultrastructural), viability, and hepatocyte-functions post thawing were observed over 7 d in culture. UW/DMSO/glucose, as a basal freezing medium, was used to investigate the additional effects of cytoprotectants: a pan-caspase inhibitor (benzyloxycarbonyl-Val-Ala-DL-Asp-fluoromethylketone [ZVAD]), an antioxidant (desferoxamine [DFO]), and a buffering and mechanical protectant (human serum albumin [HSA]) on RMBs. ZVAD (60 mM) had a beneficial effect on cell viability that was greater than with DFO (1 mM), HSA (2%), and basal freezing medium alone. Improvements in the ultrastructure of encapsulated hepatocytes and a lower degree of cell apoptosis were observed with all 3 cytoprotectants, with ZVAD tending to provide the greatest effect. Cytochrome P450 activity was significantly higher in the 3 cytoprotectant groups than with fresh microbeads. In conclusion, developing an optimized cryopreservation protocol by adding cytoprotectants such as ZVAD could improve the outcome of cryopreserved hepatocyte microbeads for future clinical use.

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“…Autologous Tax-specific CTL therapy for primary ATL has shown promise leading to prolongation of survival time [25, 26]. Very recently, promising results from phase I clinical trials against ATL using Tax peptide-pulsed DC-based vaccination have been reported at the 16 th International Conference on Human Retrovirology, June 26–30, 2013, Montreal, Canada (Suehiro et al, abstract no.…”

Section: Introductionmentioning

confidence: 99%

In vivo immunogenicity of Tax(11–19) epitope in HLA-A2/DTR transgenic mice: Implication for dendritic cell-based anti-HTLV-1 vaccine

Sagar

Masih

Schell

et al. 2014

Vaccine

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Viral oncoprotein Tax plays key roles in transformation of human T-cell leukemia virus (HTLV-1)-infected T cells leading to adult T-cell leukemia (ATL), and is the key antigen recognized during HTLV-associated myelopathy (HAM). In HLA-A2+ asymptomatic carriers as well as ATL and HAM patients, Tax(11-19) epitope exhibits immunodominance. Here, we evaluate CD8 T-cell immune response against this epitope in the presence and absence of dendritic cells (DCs) given the recent encouraging observations made with Phase 1 DC-based vaccine trial for ATL. To facilitate these studies, we first generated an HLA-A2/DTR hybrid mouse strain carrying the HLA-A2.1 and CD11c-DTR genes. We then studied CD8 T-cell immune response against Tax(11-19) epitope delivered in the absence or presence of Freund’s adjuvant and/or DCs. Overall results demonstrate that naturally presented Tax epitope could initiate an antigen-specific CD8 T cell response in vivo but failed to do so upon DC depletion. Presence of adjuvant potentiated Tax(11-19)-specific response. Elevated serum IL-6 levels coincided with depletion of DCs whereas decreased TGF-β was associated with adjuvant use. Thus, Tax(11-19) epitope is a potential candidate for the DC-based anti-HTLV-1 vaccine and the newly hybrid mouse strain could be used for investigating DC involvement in human class-I-restricted immune responses.

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Potential Contribution of a Novel Tax Epitope–Specific CD4+ T Cells to Graft-versus-Tax Effect in Adult T Cell Leukemia Patients after Allogeneic Hematopoietic Stem Cell Transplantation

Cited by 12 publications

References 50 publications

Vaccination against δ-Retroviruses: The Bovine Leukemia Virus Paradigm

Vaccination against δ-Retroviruses: The Bovine Leukemia Virus Paradigm

Cryopreservation of Hepatocyte Microbeads for Clinical Transplantation

In vivo immunogenicity of Tax(11–19) epitope in HLA-A2/DTR transgenic mice: Implication for dendritic cell-based anti-HTLV-1 vaccine

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