Research Topics
Genomes and Genes | Hideho OkadaSummaryAffiliation: University of Pittsburgh Country: USA Publications
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Publications
EphA2 as a glioma-associated antigen: a novel target for glioma vaccinesManabu Hatano
Department of Neurological Surgery, University of Pittsburgh School of Medicine and University of Pittsburgh Cancer Institute, Pittsburgh, PA 15213, USA
Neoplasia 7:717-22. 2005..Taken together, these data suggest that EphA2883-891 may be an attractive antigen epitope for molecularly targeted glioma vaccines...- Spontaneous immune responses against glioma-associated antigens in a long term survivor with malignant gliomaRyo Ueda
Department of Neurological Surgery, University of Pittsburgh School of Medicine, 200 Lothrop Street, Pittsburgh, PA 15213, USA
J Transl Med 5:68. 2007..In this report, we characterized GAA-specific CD8+ T cells and innate immune cells in a patient who has survived with anaplastic astrocytoma (AA) for over 12 years without recurrence... 
Effective immunotherapy against murine gliomas using type 1 polarizing dendritic cells--significant roles of CXCL10Mitsugu Fujita
Department of Neurological Surgery, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA
Cancer Res 69:1587-95. 2009..Collectively, these findings show the anti-CNS glioma effects of DC1-based therapy and a novel role of CXCL10 in the immunologic and therapeutic activity of DC-based cancer vaccines...- Poly-ICLC promotes the infiltration of effector T cells into intracranial gliomas via induction of CXCL10 in IFN-alpha and IFN-gamma dependent mannersXinmei Zhu
Department of Neurological Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA
Cancer Immunol Immunother 59:1401-9. 2010..Our data point to critical roles of the host-IFN-alpha and IFN-gamma pathways in the modulation of CNS glioma microenvironment, and the therapeutic effectiveness of poly-ICLC-assisted glioma vaccines... - Type17 T-cells in central nervous system autoimmunity and tumorsHideho Okada
Department of Neurological Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA
J Clin Immunol 32:802-8. 2012..The insight gained from these findings may lead to the development of novel therapeutic and prophylactic strategies for CNS autoimmunity and tumors... - MicroRNAs in immune regulation--opportunities for cancer immunotherapyHideho Okada
Department of Neurological Surgery, University of Pittsburgh School of Medicine, 200 Lothrop Street, Pittsburgh, PA 15213, USA
Int J Biochem Cell Biol 42:1256-61. 2010..We have also demonstrated that the ability of tumors to serve as targets for cytolytic effectors is regulated by miR-222 and miR-339... - Brain tumor immunotherapy with type-1 polarizing strategiesHideho Okada
University of Pittsburgh School of Medicine, Brain Tumor Program, University of Pittsburgh Cancer Institute, Pittsburgh, PA, USA
Ann N Y Acad Sci 1174:18-23. 2009..Based on these data, we have implemented a phase I/II vaccination study using type 1 polarizing DCs loaded with GAA peptides in combination with poly-ICLC in patients with recurrent malignant glioma... - Autologous glioma cell vaccine admixed with interleukin-4 gene transfected fibroblasts in the treatment of patients with malignant gliomasHideho Okada
Department of Neurological Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA
J Transl Med 5:67. 2007..The prognosis for malignant gliomas remains dismal. We addressed the safety, feasibility and preliminary clinical activity of the vaccinations using autologous glioma cells and interleukin (IL)-4 gene transfected fibroblasts... - Immunotherapeutic approaches for gliomaHideho Okada
Brain Tumor Program, University of Pittsburgh Cancer Institute, Pittsburgh, PA 15213, USA
Crit Rev Immunol 29:1-42. 2009..Finally, we discuss how each of these promising strategies can be combined to achieve clinical benefit for patients with gliomas... - Expression of glioma-associated antigens in pediatric brain stem and non-brain stem gliomasHideho Okada
Department of Neurological Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA
J Neurooncol 88:245-50. 2008..These results suggest that EphA2, IL-13Ralpha2 and Survivin are suitable targets for developing vaccine strategies for pediatric glioma... - Induction of CD8+ T-cell responses against novel glioma-associated antigen peptides and clinical activity by vaccinations with {alpha}-type 1 polarized dendritic cells and polyinosinic-polycytidylic acid stabilized by lysine and carboxymethylcellulose in Hideho Okada
G12 a Research Pavilion at the Hillman Cancer Center, 5117 Centre Ave, Pittsburgh, PA 15213 1863, USA
J Clin Oncol 29:330-6. 2011..GAAs for these peptides are EphA2, interleukin (IL)-13 receptor-α2, YKL-40, and gp100... 
Cytokine gene therapy for malignant gliomaHideho Okada
University of Pittsburgh Medical Center Cancer Institute, Department of Neurological Surgery, Brain Tumor Program, G12 a Research Pavilion at the Hillman Cancer Center, 5117 Centre Ave, Pittsburgh, PA 15213 1863, USA
Expert Opin Biol Ther 4:1609-20. 2004..Successful immunogene therapy for brain tumours requires detailed understanding of cytokine functions and the use of them at the appropriate stages/sites of the immunological milieu...- Delivery of dendritic cells engineered to secrete IFN-alpha into central nervous system tumors enhances the efficacy of peripheral tumor cell vaccines: dependence on apoptotic pathwaysNaruo Kuwashima
Department of Neurological Surgery, University of Pittsburgh School of Medicine, PA 15213, USA
J Immunol 175:2730-40. 2005.... - Dicer-regulated microRNAs 222 and 339 promote resistance of cancer cells to cytotoxic T-lymphocytes by down-regulation of ICAM-1Ryo Ueda
Department of Neurological Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA
Proc Natl Acad Sci U S A 106:10746-51. 2009..This study suggests development of novel miR-targeted therapy to promote cytolysis of tumor cells... - Systemic inhibition of transforming growth factor-beta in glioma-bearing mice improves the therapeutic efficacy of glioma-associated antigen peptide vaccinesRyo Ueda
Department of Neurological Surgery, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA
Clin Cancer Res 15:6551-9. 2009..We hypothesized that inhibition of TGF-beta would improve the efficacy of vaccines targeting glioma-associated antigen (GAA)-derived CTL epitopes by reversal of immunosuppression... - Inhibition of STAT3 promotes the efficacy of adoptive transfer therapy using type-1 CTLs by modulation of the immunological microenvironment in a murine intracranial gliomaMitsugu Fujita
Department of Neurological Surgery and Brain Tumor Program, University of Pittsburgh School of Medicine, Pittsburgh, PA 15232, USA
J Immunol 180:2089-98. 2008.... - Toll like receptor-3 ligand poly-ICLC promotes the efficacy of peripheral vaccinations with tumor antigen-derived peptide epitopes in murine CNS tumor modelsXinmei Zhu
Department of Neurological Surgery, University of Pittsburgh School of Medicine, Pittsburgh, USA
J Transl Med 5:10. 2007.... - IL-4 suppresses very late antigen-4 expression which is required for therapeutic Th1 T-cell trafficking into tumorsKotaro Sasaki
Department of Dermatology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA
J Immunother 32:793-802. 2009..These data suggest that treatment strategies capable of sustaining/enhancing VLA-4/VLA-6 expression on Th1 effector cells may yield improved clinical efficacy in the cancer setting... - Identification of interleukin-13 receptor alpha2 peptide analogues capable of inducing improved antiglioma CTL responsesJunichi Eguchi
Department of Neurological Surgery, University of Pittsburgh School of Medicine, USA
Cancer Res 66:5883-91. 2006..These findings indicate highly immunogenic IL-13Ralpha2 peptide analogues may be useful for the development of vaccines capable of effectively expanding IL-13Ralpha2-specific, tumor-reactive CTLs in glioma patients... - IL-4-transfected tumor cell vaccines activate tumor-infiltrating dendritic cells and promote type-1 immunityJunichi Eguchi
Department of Neurological Surgery, University of Pittsburgh School of Medicine, PA 15213, USA
J Immunol 174:7194-201. 2005..These results suggest that vaccines consisting of tumor cells engineered to produce the type 2 cytokine, IL-4, critically depend on type 1 immunity for their observed therapeutic efficacy... - IL-4 inhibits VLA-4 expression on Tc1 cells resulting in poor tumor infiltration and reduced therapy benefitKotaro Sasaki
Department of Dermatology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA
Eur J Immunol 38:2865-73. 2008..These results suggest a novel suppressive mechanism for IL-4 that limits Tc1 efficacy via preventing their recruitment into tumors... - Adoptive transfer of type 1 CTL mediates effective anti-central nervous system tumor response: critical roles of IFN-inducible protein-10Fumihiko Nishimura
Department of Neurological Surgery, University of Pittsburgh Cancer Institute, Pennsylvania 15213, USA
Cancer Res 66:4478-87. 2006..These data suggest that Tc1-based adoptive transfer therapy may represent an effective modality for CNS tumors, particularly when combined with strategies that promote a type 1 polarized tumor microenvironment... - Epidermal growth factor receptor-transfected bone marrow stromal cells exhibit enhanced migratory response and therapeutic potential against murine brain tumorsHidemitsu Sato
Department of Neurological Surgery, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15213-1863, USA
Cancer Gene Ther 12:757-68. 2005..These data indicate that EGFR-MSCs may serve as attractive vehicles for infiltrating brain malignancies such as malignant gliomas... - The characterization of tumor apoptosis after experimental radiosurgeryTimothy F Witham
Department of Neurological Surgery, University of Pittsburgh Medical Center, Pittsburgh, PA 15213-2582, USA
Stereotact Funct Neurosurg 83:17-24. 2005..The time course of this radiobiologic phenomenon begins at approximately 6 h following radiosurgery, continues up to 48 h, and begins to decline by 72 h... - miR-17-92 expression in differentiated T cells - implications for cancer immunotherapyKotaro Sasaki
Department of Immunology, University of Pittsburgh School of Medicine, PA 15213, USA
J Transl Med 8:17. 2010..We identified miRs differentially regulated between type-1 and type-2 T cells, and determined how the expression of such miRs is regulated... - Autologous glioma cell vaccine admixed with interleukin-4 gene transfected fibroblasts in the treatment of recurrent glioblastoma: preliminary observations in a patient with a favorable response to therapyHideho Okada
Department of Neurological Surgery, University of Pittsburgh School of Medicine, PA, USA
J Neurooncol 64:13-20. 2003..While it is premature to assess effectiveness of the vaccine, this initial patient's course suggested a transient response to the vaccine, and he survived 10 months after treatment... - Delivery of interferon-alpha transfected dendritic cells into central nervous system tumors enhances the antitumor efficacy of peripheral peptide-based vaccinesHideho Okada
Departments of Neurological Surgery, University of Pittsburgh School of Medicine, PA 15213, USA
Cancer Res 64:5830-8. 2004..On the basis of these results, we believe that local expression of IFN-alpha by DCs within the intracranial tumor site may enhance the clinical efficacy of peripheral vaccine approaches for brain tumors... - Stat6 signaling suppresses VLA-4 expression by CD8+ T cells and limits their ability to infiltrate tumor lesions in vivoKotaro Sasaki
Department of Dermatology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA
J Immunol 181:104-8. 2008..These results suggest that Stat6-signaling is necessary and sufficient to restrict CD8+ T cell expression of VLA-4 (by IL-4), thereby serving as a regulator for CD8+ T cell infiltration into tumors... - Role of type 1 IFNs in antiglioma immunosurveillance--using mouse studies to guide examination of novel prognostic markers in humansMitsugu Fujita
Department of Neurological Surgery, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA
Clin Cancer Res 16:3409-19. 2010..We hypothesized that the type 1 IFNs would play a pivotal role in antiglioma immunosurveillance through promotion of type 1 adaptive immunity and suppression of immunoregulatory cells... - Preferential expression of very late antigen-4 on type 1 CTL cells plays a critical role in trafficking into central nervous system tumorsKotaro Sasaki
Department of Dermatology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA
Cancer Res 67:6451-8. 2007.... - Treatment-enhanced CD4+Foxp3+ glucocorticoid-induced TNF receptor family related high regulatory tumor-infiltrating T cells limit the effectiveness of cytokine-based immunotherapyAklile Berhanu
Department of Immunology, University of Pittsburgh School of Medicine, 200 Lothrop Street, Pittsburgh, PA 15213, USA
J Immunol 178:3400-8. 2007..Importantly, in vivo depletion of CD4+ T cells resulted in the ability of previously ineffective, rFL plus rGM-CSF therapy-induced CD8+ T cells to now mediate tumor regression... - Helper function of memory CD8+ T cells: heterologous CD8+ T cells support the induction of therapeutic cancer immunityYutaro Nakamura
Department of Surgery, University of Pittsburgh, Eye and Ear Institute, PA 15213 1863, USA
Cancer Res 67:10012-8. 2007.... - Expression of a soluble transforming growth factor-beta (TGFbeta) receptor reduces tumorigenicity by regulating natural killer (NK) cell activity against 9L gliosarcoma in vivoTimothy F Witham
Brain Tumor Center, University of Pittsburgh Cancer Institute, Pittsburgh, PA 15213-1863, USA
J Neurooncol 64:63-9. 2003..Finally, we determined that elimination of CD161+ cells resulted in comparable growth of 9L-neo and 9L-TGFbeta sr in vivo, indicating that NK or NK-like cells were responsible for the anti-tumor effects in this model... - 7-Hydroxystaurosporine-induced apoptosis in 9L glioma cells provides an effective antigen source for dendritic cells and yields a potent vaccine strategy in an intracranial glioma modelTimothy F Witham
Department of Neurological Surgery, University of Pittsburgh School of Medicine, Pennsylvania, USA
Neurosurgery 50:1327-34; discussion 1334-5. 2002.... - Identification of a novel HLA-A*0201-restricted, cytotoxic T lymphocyte epitope in a human glioma-associated antigen, interleukin 13 receptor alpha2 chainFumiyoshi Okano
Department of Surgery, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania 15213, USA
Clin Cancer Res 8:2851-5. 2002..Interleukin 13 receptor alpha2-chain (IL-13Ralpha2) has been reported to be abundantly and specifically overexpressed in glioblastoma multiforme. Here we report the identification of a CTL epitope derived from the IL-13Ralpha2... - LOH in the HLA Class I Region at 6p21 Is Associated with Shorter Survival in Newly Diagnosed Adult GlioblastomaJacky T Yeung
Authors Affiliations Departments of Neurological Surgery, Pathology, Surgery and Immunology, and Pediatrics, University of Pittsburgh School of Medicine Department of Biostatistics, Graduate School of Public Health and Brain Tumor Program and Biostatistics Facility, University of Pittsburgh Cancer Institute, University of Pittsburgh, Pittsburgh, Pennsylvania
Clin Cancer Res 19:1816-26. 2013..In this study, we examined the prevalence of these LOH events and their relations with overall survival in GBM... - Dendritic cells in cancer immunotherapy: vaccines or autologous transplants?Pawel Kalinski
Department of Surgery, University of Pittsburgh, Pittsburgh, PA 15213 1863, USA
Immunol Res 50:235-47. 2011.... - Polarized dendritic cells as cancer vaccines: directing effector-type T cells to tumorsPawel Kalinski
Department of Surgery, University of Pittsburgh, Pittsburgh, PA 15213, United States
Semin Immunol 22:173-82. 2010..These developments allow for selective induction of tumor-specific T cells with desirable effector functions and tumor-relevant homing properties and to direct the desirable types of immune cells to tumors... - Systemic delivery of neutralizing antibody targeting CCL2 for glioma therapyXinmei Zhu
Department of Neurological Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA
J Neurooncol 104:83-92. 2011..0359). These observations provide support for development of mAb-based CCL2 blockade strategies in combination with the current standard TMZ-based chemotherapy for treatment of malignant gliomas... - COX-2 blockade suppresses gliomagenesis by inhibiting myeloid-derived suppressor cellsMitsugu Fujita
Brain Tumor Program, University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania, USA
Cancer Res 71:2664-74. 2011..Taken together, our findings show that the COX-2 pathway promotes gliomagenesis by directly supporting systemic development of MDSCs and their accumulation in the TME, where they limit CTL infiltration... - Myeloid-derived suppressor cells (MDSCs) in gliomas and glioma-developmentGary Kohanbash
Department of Infectious Diseases and Microbiology, University of Pittsburgh Graduate School of Public Health, Pittsburgh, PA 15261, USA
Immunol Invest 41:658-79. 2012..The insight gained from these findings may lead to the development of novel immunotherapeutic strategies for gliomas... - Expression of antigen processing and presenting molecules in brain metastasis of breast cancerYan Liu
Brain Tumor Program, University of Pittsburgh Cancer Institute, Pittsburgh, PA, USA
Cancer Immunol Immunother 61:789-801. 2012..Taken together, our data suggest that patients with low or defective TAP1 or calnexin in primary breast cancers may be at higher risks for developing brain metastasis due to the defects in T cell-based immunosurveillance... - MicroRNAs and STAT interplayGary Kohanbash
Department of Infectious Diseases and Microbiology, University of Pittsburgh Graduate School of Public Health, Pittsburgh, PA 15261, USA
Semin Cancer Biol 22:70-5. 2012..As we learn more about miR pathways, we gain the opportunity to manipulate them in cancer cells to slow down growth or increase their susceptibility anti-tumor immunity... - Intratumoral delivery of dendritic cells engineered to secrete both interleukin (IL)-12 and IL-18 effectively treats local and distant disease in association with broadly reactive Tc1-type immunityTomohide Tatsumi
Department of Surgery, University of Pittsburgh School of Medicine, The Hillman Cancer Center, 5117 Center Avenue, Pittsburgh, PA 15213, USA
Cancer Res 63:6378-86. 2003.... - Gene therapy and biologic therapy with interleukin-4Hideho Okada
University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania 15213 1863, USA
Curr Gene Ther 2:437-50. 2002..This review discusses biological properties and therapeutic applications of IL-4, particularly when it is delivered as a transgene in the settings of gene therapy... - Biologic therapy for brain cancers--based on cellular and immunobiologyHideho Okada
Department of Neurosurgery and Surgery, University of Pittsburgh Medical Center Cancer Institute, G12 aResearch Pavilion at the Hillman Cancer Center, Pittsburgh, PA, 15213 1863, USA
Yonsei Med J 45:68-70. 2004.... - Vaccines targeting tumor blood vessel antigens promote CD8(+) T cell-dependent tumor eradication or dormancy in HLA-A2 transgenic miceXi Zhao
Department of Dermatology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA
J Immunol 188:1782-8. 2012..This suggests that the vaccine-induced anti-TBVA T cell repertoire can mediate the clinically preferred outcomes of either effectively eradicating tumors or policing a state of (occult) tumor dormancy... - Absence of Stat1 in donor CD4⁺ T cells promotes the expansion of Tregs and reduces graft-versus-host disease in miceHuihui Ma
Department of Medicine, Division of Hematology Oncology, Hematologic Malignancies Program, University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania 15213 1863, USA
J Clin Invest 121:2554-69. 2011..These observations demonstrate that Stat1 is a regulator of Tregs and that targeting Stat1 in CD4+ T cells may facilitate in vitro and in vivo expansion of Tregs for therapeutic use... - Integration of epidemiology, immunobiology, and translational research for brain tumorsHideho Okada
University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania
Ann N Y Acad Sci 1284:17-23. 2013..Future research will hopefully better integrate epidemiological, immunobiological, and translational techniques to develop novel, preventive approaches for malignant gliomas... - Increased expression of tumor-associated antigens in pediatric and adult ependymomas: implication for vaccine therapyJacky T Yeung
Department of Neurological Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA
J Neurooncol 111:103-11. 2013..Pediatric and adult ependymomas frequently express EphA2, IL-13Rα2, and Survivin. This provides the basis for the utilization of an established multiple peptide vaccine for ependymoma in a clinical trial setting... - Glioma-associated hyaluronan induces apoptosis in dendritic cells via inducible nitric oxide synthase: implications for the use of dendritic cells for therapy of gliomasTianbing Yang
Brain Tumor Center, University of Pittsburgh Cancer Institute, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15213, USA
Cancer Res 62:2583-91. 2002..These data indicate that HA expressed by gliomas may contribute to their immunosuppressive effects by promoting apoptosis among professional antigen-presenting cells such as DCs via iNOS induction after CD44-HA interactions... - Antigenic profiling of glioma cells to generate allogeneic vaccines or dendritic cell-based therapeuticsJian Gang Zhang
Diagnostic and Molecular Health Care Group, Veterans Affairs Medical Center, Long Beach, CA 90822, USA
Clin Cancer Res 13:566-75. 2007.... - Progression-associated genes in astrocytoma identified by novel microarray gene expression data reanalysisTobey J Macdonald
Center for Cancer and Immunology Research, Children s Research Institute, Department of Hematology Oncology, Children s National Medical Center, Washington, DC, USA
Methods Mol Biol 377:203-22. 2007..Further investigation is needed to evaluate the role of APOD, as well as the other genes identified, in malignant astrocytoma development... - Effective induction of antiglioma cytotoxic T cells by coadministration of interferon-beta gene vector and dendritic cellsNorimoto Nakahara
Department of Bio-Medicine, Nagoya University School of Medicine, Nagoya, Japan
Cancer Gene Ther 10:549-58. 2003..Suppression of the tumor growth by this combinational therapy was superior to treatment with DC or IFN-beta gene solely. This combination may constitute a new therapeutic strategy to induce potent antiglioma immune responses... - [Immunotherapy for brain tumor: don't get "Lost in Translation"]Hideho Okada
Department of Neurosurgery and Surgery, University of Pittsburgh Medical Center/Cancer Institute, PA 15213-1863, USA
No Shinkei Geka 33:433-42. 2005
Research Grants
- Giloma Vaccines in Combination with Poly-ICLCHideho Okada; Fiscal Year: 2009....
- Vaccination With Peptide-loaded alphaDC1s For Malignant GliomasHideho Okada; Fiscal Year: 2007..Information from this pilot study will establish a basis to design subsequent trials with patient populations in which more significant clinical benefit might be realized. ..
- Giloma Vaccines in Combination with Poly-ICLCHideho Okada; Fiscal Year: 2007....