The Experts below are selected from a list of 12045 Experts worldwide ranked by ideXlab platform
Duane Mitchell - One of the best experts on this subject based on the ideXlab platform.
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once twice three times a finding reproducibility of Dendritic Cell Vaccine trials targeting cytomegalovirus in glioblastoma
Clinical Cancer Research, 2020Co-Authors: Kristen A Batich, Patrick Healy, James E Herndon, Duane Mitchell, John H SampsonAbstract:Despite standard of care for glioblastoma, including gross total resection, high-dose radiation, and dose-limited chemotherapy, this tumor remains one of the most aggressive and therapeutically challenging. The relatively small number of patients with this diagnosis compared with more common solid tumors in clinical trials commits new glioblastoma therapies to testing in small, underpowered, nonrandomized settings. Among approximately 200 registered glioblastoma trials identified between 2005 and 2015, nearly half were single-arm studies with sample sizes not exceeding 50 patients. These constraints have made demonstrating efficacy for novel therapies difficult in glioblastoma and other rare and aggressive cancers. Novel immunotherapies for glioblastoma such as vaccination with Dendritic Cells (DC) have yielded mixed results in clinical trials. To address limited numbers, we sequentially conducted three separate clinical trials utilizing cytomegalovirus (CMV)-specific DC Vaccines in patients with newly diagnosed glioblastoma whereby each follow-up study had nearly doubled in sample size. Follow-up data from the first blinded, randomized phase II clinical trial (NCT00639639) revealed that nearly one third of this cohort is without tumor recurrence at 5 years from diagnosis. A second clinical trial (NCT00639639) resulted in a 36% survival rate at 5 years from diagnosis. Results of the first two-arm trial (NCT00639639) showed increased migration of the DC Vaccine to draining lymph nodes, and this increased migration has been recapitulated in our larger confirmatory clinical study (NCT02366728). We have now observed that nearly one third of the glioblastoma study patient population receiving CMV-specific DC Vaccines results in exceptional long-term survivors.
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the development of Dendritic Cell Vaccine based immunotherapies for glioblastoma
Seminars in Immunopathology, 2017Co-Authors: David A Reardon, Duane MitchellAbstract:In this review, we focus on the biologic advantages of Dendritic Cell-based vaccinations as a therapeutic strategy for cancer as well as preclinical and emerging clinical data associated with such approaches for glioblastoma patients.
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Gene-modified Dendritic Cell Vaccines for cancer.
Cytotherapy, 2016Co-Authors: Rebecca Abraham, Duane MitchellAbstract:Dendritic Cell (DC) Vaccines are an immunotherapeutic approach to cancer treatment that use the antigen-presentation machinery of DCs to activate an endogenous anti-tumor response. In this treatment strategy, DCs are cultured ex vivo, exposed to tumor antigens and administered to the patient. The ex vivo culturing provides a unique and powerful opportunity to modify and enhance the DCs. As such, a variety of genetic engineering approaches have been employed to optimize DC Vaccines, including the introduction of messenger RNA and small interfering RNA, viral gene transduction, and even fusion with whole tumor Cells. In general, these modifications aim to improve targeting, enhance immunogenicity, and reduce susceptibility to the immunosuppressive tumor microenvironment. It has been demonstrated that several of these modifications can be employed in tandem, allowing for fine-tuning and optimization of the DC Vaccine across multiple metrics. Thus, the application of genetic engineering techniques to the Dendritic Cell Vaccine platform has the potential to greatly enhance its efficacy in the clinic.
Nathaniel R. Landau - One of the best experts on this subject based on the ideXlab platform.
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Lentiviral-Vector-Based Dendritic Cell Vaccine Synergizes with Checkpoint Blockade to Clear Chronic Viral Infection.
Molecular therapy : the journal of the American Society of Gene Therapy, 2020Co-Authors: Thomas D. Norton, Takuya Tada, Rebecca Leibowitz, Verena Van Der Heide, Dirk Homann, Nathaniel R. LandauAbstract:Dendritic Cell Vaccines are a promising strategy for the treatment of cancer and infectious diseases but have met with mixed success. We report on a lentiviral vector-based Dendritic Cell Vaccine strategy that generates a cluster of differentiation 8 (CD8) T Cell response that is much stronger than that achieved by standard peptide-pulsing approaches. The strategy was tested in the mouse lymphocytic choriomeningitis virus (LCMV) model. Bone marrow-derived Dendritic Cells from SAMHD1 knockout mice were transduced with a lentiviral vector expressing the GP33 major-histocompatibility-complex (MHC)-class-I-restricted peptide epitope and CD40 ligand (CD40L) and injected into wild-type mice. The mice were highly protected against acute and chronic variant CL-13 LCMVs, resulting in a 100-fold greater decrease than that achieved with peptide epitope-pulsed Dendritic Cells. Inclusion of an MHC-class-II-restricted epitope in the lentiviral vector further increased the CD8 T Cell response and resulted in antigen-specific CD8 T Cells that exhibited a phenotype associated with functional cytotoxic T Cells. The vaccination synergized with checkpoint blockade to reduce the viral load of mice chronically infected with CL-13 to an undetectable level. The strategy improves upon current Dendritic Cell Vaccine strategies; is applicable to the treatment of disease, including AIDS and cancer; and supports the utility of Vpx-containing vectors.
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lentiviral vector based Dendritic Cell Vaccine suppresses hiv replication in humanized mice
Molecular Therapy, 2019Co-Authors: Thomas D. Norton, Takuya Tada, Anjie Zhen, Jennifer Kim, Scott G Kitchen, Nathaniel R. LandauAbstract:HIV-1-infected individuals are treated with lifelong antiretroviral drugs to control the infection. A means to strengthen the antiviral T Cell response might allow them to control viral loads without antiretroviral drugs. We report the development of a lentiviral vector-based Dendritic Cell (DC) Vaccine in which HIV-1 antigen is co-expressed with CD40 ligand (CD40L) and a soluble, high-affinity programmed Cell death 1 (PD-1) dimer. CD40L activates the DCs, whereas PD-1 binds programmed death ligand 1 (PD-L1) to prevent checkpoint activation and strengthen the cytotoxic T lymphocyte (CTL) response. The injection of humanized mice with DCs transduced with vector expressing CD40L and the HIV-1 SL9 epitope induced antigen-specific T Cell proliferation and memory differentiation. Upon HIV-1 challenge of vaccinated mice, viral load was suppressed by 2 logs for 6 weeks. Introduction of the soluble PD-1 dimer into a vector that expressed full-length HIV-1 proteins accelerated the antiviral response. The results support development of this approach as a therapeutic Vaccine that might allow HIV-1-infected individuals to control virus replication without antiretroviral therapy.
Masakazu Yamamoto - One of the best experts on this subject based on the ideXlab platform.
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Postoperative Dendritic Cell Vaccine plus activated T-Cell transfer improves the survival of patients with invasive hepatoCellular carcinoma
Human vaccines & immunotherapeutics, 2014Co-Authors: Koichi Shimizu, Yoshihito Kotera, Atsushi Aruga, Nobuhiro Takeshita, Ken Takasaki, Satoshi Katagiri, Shunichi Ariizumi, Yutaka Takahashi, Kenji Yoshitoshi, Masakazu YamamotoAbstract:The recurrence rate after surgery in patients with hepatoCellular carcinoma (HCC) is very high, while prognosis is quite poor. However, there is no standard treatment to prevent recurrence of HCC after a curative operation. In this study, we investigated the clinical utilization of an autologous tumor lysate-pulsed Dendritic Cell Vaccine plus ex vivo activated T Cell transfer (ATVAC) in an adjuvant setting for postoperative HCC as a non-randomized controlled trial. Ninety-four patients with invasive HCC received informed consent information regarding the study, and 42 opted to have the ATVAC after surgery. Their recurrence-free survival (RFS) and overall survival (OS) were measured after 5 years and compared with those of 52 patients who selected to have the curative operation alone. The median RFS and OS were 24.5 months and 97.7 months in the patients receiving adjuvant ATVAC and 12.6 months and 41.0 months in the group receiving surgery alone (P = 0.011 and 0.029). In the treated group, patients with p...
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clinical utilization of postoperative Dendritic Cell Vaccine plus activated t Cell transfer in patients with intrahepatic cholangiocarcinoma
Journal of Hepato-biliary-pancreatic Sciences, 2012Co-Authors: Koichi Shimizu, Yoshihito Kotera, Atsushi Aruga, Nobuhiro Takeshita, Ken Takasaki, Masakazu YamamotoAbstract:The prognosis of patients with intrahepatic cholangiocarcinoma (ICC) is extremely poor and the recurrence rate after curative operation is very high. There is no standard treatment to prevent recurrence of ICC. In this study, we investigated the clinical utilization of a Dendritic Cell Vaccine plus activated T-Cell transfer in an adjuvant setting for postoperative ICC. 36 patients with ICC were vaccinated at least 3 times with autologous tumor lysate pulsed Dendritic Cells plus ex-vivo activated T-Cell transfer. The 5-year progression-free survival (PFS) and overall survival (OS) were measured and compared with those of 26 patients who received the curative operation alone as a concurrent control. The registration number was UMIN000005820. The median PFS and OS were 18.3 and 31.9 months in the patients receiving adjuvant immunotherapy and 7.7 and 17.4 months in the group receiving surgery alone (p = 0.005 and 0.022, respectively). In the treated group, patients whose skin reactions were 3 cm or more at the Vaccine site showed dramatically better prognosis (PFS p < 0.001, OS p = 0.001). A postoperative Dendritic Cell Vaccine plus activated T-Cell transfer would be a feasible and effective treatment for preventing recurrence and achieving long-term survival in ICC patients.
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Clinical utilization of postoperative Dendritic Cell Vaccine plus activated T‐Cell transfer in patients with intrahepatic cholangiocarcinoma
Journal of hepato-biliary-pancreatic sciences, 2011Co-Authors: Koichi Shimizu, Yoshihito Kotera, Atsushi Aruga, Nobuhiro Takeshita, Ken Takasaki, Masakazu YamamotoAbstract:The prognosis of patients with intrahepatic cholangiocarcinoma (ICC) is extremely poor and the recurrence rate after curative operation is very high. There is no standard treatment to prevent recurrence of ICC. In this study, we investigated the clinical utilization of a Dendritic Cell Vaccine plus activated T-Cell transfer in an adjuvant setting for postoperative ICC. 36 patients with ICC were vaccinated at least 3 times with autologous tumor lysate pulsed Dendritic Cells plus ex-vivo activated T-Cell transfer. The 5-year progression-free survival (PFS) and overall survival (OS) were measured and compared with those of 26 patients who received the curative operation alone as a concurrent control. The registration number was UMIN000005820. The median PFS and OS were 18.3 and 31.9 months in the patients receiving adjuvant immunotherapy and 7.7 and 17.4 months in the group receiving surgery alone (p = 0.005 and 0.022, respectively). In the treated group, patients whose skin reactions were 3 cm or more at the Vaccine site showed dramatically better prognosis (PFS p
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Dendritic Cell Vaccine for intrahepatic cholangio Cellular carcinoma--a study of relationship between immuno-reaction and clinical outcome
Gan to kagaku ryoho. Cancer & chemotherapy, 2009Co-Authors: Yoshihito Kotera, Atsushi Aruga, Yumi Kougen, Masakazu YamamotoAbstract:The clinical outcome of intra-hepatic cholangioCelluler carcinoma (ICC) is very poor. To prevent a tumor relapse after curative operation, we employed the combination therapy of adaptive transfer of anti-CD3 activated T Cells and Dendritic Cell Vaccine therapy (DC-CAT therapy) since 2000. During DC-CAT therapy, about a half of patient revealed skin reaction positive. Moreover, the patient who had a skin reaction showed a significantly good clinical outcome. In this study, we investigated the difference between skin reaction positive and negative checking with the surface markers of T Cells. The patient who had skin reaction positive increased the number of lymphocyte. Especially, CD8 positive T Cells were increased about 2 folds in number before the DC-CAT therapy, and decreased Foxp3 positive regulatory T Cells. Our data suggest that increasing cytotoxic T Cells and decreasing regulatory T Cells made the difference of the clinical outcome such as a disease free survival rate and overall survival rate after curative operation for ICC patient.
Thomas D. Norton - One of the best experts on this subject based on the ideXlab platform.
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Lentiviral-Vector-Based Dendritic Cell Vaccine Synergizes with Checkpoint Blockade to Clear Chronic Viral Infection.
Molecular therapy : the journal of the American Society of Gene Therapy, 2020Co-Authors: Thomas D. Norton, Takuya Tada, Rebecca Leibowitz, Verena Van Der Heide, Dirk Homann, Nathaniel R. LandauAbstract:Dendritic Cell Vaccines are a promising strategy for the treatment of cancer and infectious diseases but have met with mixed success. We report on a lentiviral vector-based Dendritic Cell Vaccine strategy that generates a cluster of differentiation 8 (CD8) T Cell response that is much stronger than that achieved by standard peptide-pulsing approaches. The strategy was tested in the mouse lymphocytic choriomeningitis virus (LCMV) model. Bone marrow-derived Dendritic Cells from SAMHD1 knockout mice were transduced with a lentiviral vector expressing the GP33 major-histocompatibility-complex (MHC)-class-I-restricted peptide epitope and CD40 ligand (CD40L) and injected into wild-type mice. The mice were highly protected against acute and chronic variant CL-13 LCMVs, resulting in a 100-fold greater decrease than that achieved with peptide epitope-pulsed Dendritic Cells. Inclusion of an MHC-class-II-restricted epitope in the lentiviral vector further increased the CD8 T Cell response and resulted in antigen-specific CD8 T Cells that exhibited a phenotype associated with functional cytotoxic T Cells. The vaccination synergized with checkpoint blockade to reduce the viral load of mice chronically infected with CL-13 to an undetectable level. The strategy improves upon current Dendritic Cell Vaccine strategies; is applicable to the treatment of disease, including AIDS and cancer; and supports the utility of Vpx-containing vectors.
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lentiviral vector based Dendritic Cell Vaccine suppresses hiv replication in humanized mice
Molecular Therapy, 2019Co-Authors: Thomas D. Norton, Takuya Tada, Anjie Zhen, Jennifer Kim, Scott G Kitchen, Nathaniel R. LandauAbstract:HIV-1-infected individuals are treated with lifelong antiretroviral drugs to control the infection. A means to strengthen the antiviral T Cell response might allow them to control viral loads without antiretroviral drugs. We report the development of a lentiviral vector-based Dendritic Cell (DC) Vaccine in which HIV-1 antigen is co-expressed with CD40 ligand (CD40L) and a soluble, high-affinity programmed Cell death 1 (PD-1) dimer. CD40L activates the DCs, whereas PD-1 binds programmed death ligand 1 (PD-L1) to prevent checkpoint activation and strengthen the cytotoxic T lymphocyte (CTL) response. The injection of humanized mice with DCs transduced with vector expressing CD40L and the HIV-1 SL9 epitope induced antigen-specific T Cell proliferation and memory differentiation. Upon HIV-1 challenge of vaccinated mice, viral load was suppressed by 2 logs for 6 weeks. Introduction of the soluble PD-1 dimer into a vector that expressed full-length HIV-1 proteins accelerated the antiviral response. The results support development of this approach as a therapeutic Vaccine that might allow HIV-1-infected individuals to control virus replication without antiretroviral therapy.
Atsushi Aruga - One of the best experts on this subject based on the ideXlab platform.
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Postoperative Dendritic Cell Vaccine plus activated T-Cell transfer improves the survival of patients with invasive hepatoCellular carcinoma
Human vaccines & immunotherapeutics, 2014Co-Authors: Koichi Shimizu, Yoshihito Kotera, Atsushi Aruga, Nobuhiro Takeshita, Ken Takasaki, Satoshi Katagiri, Shunichi Ariizumi, Yutaka Takahashi, Kenji Yoshitoshi, Masakazu YamamotoAbstract:The recurrence rate after surgery in patients with hepatoCellular carcinoma (HCC) is very high, while prognosis is quite poor. However, there is no standard treatment to prevent recurrence of HCC after a curative operation. In this study, we investigated the clinical utilization of an autologous tumor lysate-pulsed Dendritic Cell Vaccine plus ex vivo activated T Cell transfer (ATVAC) in an adjuvant setting for postoperative HCC as a non-randomized controlled trial. Ninety-four patients with invasive HCC received informed consent information regarding the study, and 42 opted to have the ATVAC after surgery. Their recurrence-free survival (RFS) and overall survival (OS) were measured after 5 years and compared with those of 52 patients who selected to have the curative operation alone. The median RFS and OS were 24.5 months and 97.7 months in the patients receiving adjuvant ATVAC and 12.6 months and 41.0 months in the group receiving surgery alone (P = 0.011 and 0.029). In the treated group, patients with p...
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clinical utilization of postoperative Dendritic Cell Vaccine plus activated t Cell transfer in patients with intrahepatic cholangiocarcinoma
Journal of Hepato-biliary-pancreatic Sciences, 2012Co-Authors: Koichi Shimizu, Yoshihito Kotera, Atsushi Aruga, Nobuhiro Takeshita, Ken Takasaki, Masakazu YamamotoAbstract:The prognosis of patients with intrahepatic cholangiocarcinoma (ICC) is extremely poor and the recurrence rate after curative operation is very high. There is no standard treatment to prevent recurrence of ICC. In this study, we investigated the clinical utilization of a Dendritic Cell Vaccine plus activated T-Cell transfer in an adjuvant setting for postoperative ICC. 36 patients with ICC were vaccinated at least 3 times with autologous tumor lysate pulsed Dendritic Cells plus ex-vivo activated T-Cell transfer. The 5-year progression-free survival (PFS) and overall survival (OS) were measured and compared with those of 26 patients who received the curative operation alone as a concurrent control. The registration number was UMIN000005820. The median PFS and OS were 18.3 and 31.9 months in the patients receiving adjuvant immunotherapy and 7.7 and 17.4 months in the group receiving surgery alone (p = 0.005 and 0.022, respectively). In the treated group, patients whose skin reactions were 3 cm or more at the Vaccine site showed dramatically better prognosis (PFS p < 0.001, OS p = 0.001). A postoperative Dendritic Cell Vaccine plus activated T-Cell transfer would be a feasible and effective treatment for preventing recurrence and achieving long-term survival in ICC patients.
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Clinical utilization of postoperative Dendritic Cell Vaccine plus activated T‐Cell transfer in patients with intrahepatic cholangiocarcinoma
Journal of hepato-biliary-pancreatic sciences, 2011Co-Authors: Koichi Shimizu, Yoshihito Kotera, Atsushi Aruga, Nobuhiro Takeshita, Ken Takasaki, Masakazu YamamotoAbstract:The prognosis of patients with intrahepatic cholangiocarcinoma (ICC) is extremely poor and the recurrence rate after curative operation is very high. There is no standard treatment to prevent recurrence of ICC. In this study, we investigated the clinical utilization of a Dendritic Cell Vaccine plus activated T-Cell transfer in an adjuvant setting for postoperative ICC. 36 patients with ICC were vaccinated at least 3 times with autologous tumor lysate pulsed Dendritic Cells plus ex-vivo activated T-Cell transfer. The 5-year progression-free survival (PFS) and overall survival (OS) were measured and compared with those of 26 patients who received the curative operation alone as a concurrent control. The registration number was UMIN000005820. The median PFS and OS were 18.3 and 31.9 months in the patients receiving adjuvant immunotherapy and 7.7 and 17.4 months in the group receiving surgery alone (p = 0.005 and 0.022, respectively). In the treated group, patients whose skin reactions were 3 cm or more at the Vaccine site showed dramatically better prognosis (PFS p
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Dendritic Cell-based cancer immunotherapy
Nihon rinsho. Japanese journal of clinical medicine, 2010Co-Authors: Atsushi ArugaAbstract:Dendritic Cell is the most effective antigen presenting Cells in human. We performed a couple of Dendritic Cell-based cancer immunotherapy in Tokyo Women's Medical University. Autologous tumor lysates or synthetic peptides are pulsed with Dendritic Cells to make the Dendritic Cell Vaccine. Tumor-pulsed Dendritic Cell Vaccine (TP-DC) or peptide pulsed Dendritic Cell Vaccine (PP-DC) are safe and useful in the patients with advanced cancer. Antigen unpulsed immature Dendritic Cell could work at a cancer Vaccine when they inject into tumors in vivo. Dendritic Cell-activated T Cells (DCAT) in vitro are also useful tools for cancer treatment. In order to obtain a good evidence of Dendritic Cell-based immunotherapy, we need to perform the randomized trial near the future.
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Dendritic Cell Vaccine for intrahepatic cholangio Cellular carcinoma--a study of relationship between immuno-reaction and clinical outcome
Gan to kagaku ryoho. Cancer & chemotherapy, 2009Co-Authors: Yoshihito Kotera, Atsushi Aruga, Yumi Kougen, Masakazu YamamotoAbstract:The clinical outcome of intra-hepatic cholangioCelluler carcinoma (ICC) is very poor. To prevent a tumor relapse after curative operation, we employed the combination therapy of adaptive transfer of anti-CD3 activated T Cells and Dendritic Cell Vaccine therapy (DC-CAT therapy) since 2000. During DC-CAT therapy, about a half of patient revealed skin reaction positive. Moreover, the patient who had a skin reaction showed a significantly good clinical outcome. In this study, we investigated the difference between skin reaction positive and negative checking with the surface markers of T Cells. The patient who had skin reaction positive increased the number of lymphocyte. Especially, CD8 positive T Cells were increased about 2 folds in number before the DC-CAT therapy, and decreased Foxp3 positive regulatory T Cells. Our data suggest that increasing cytotoxic T Cells and decreasing regulatory T Cells made the difference of the clinical outcome such as a disease free survival rate and overall survival rate after curative operation for ICC patient.