• Bio-derived nanovaccine
• GelMA gel
• cellular immunity
• glioma
• microneedle vaccine

• glioma
• glioma vaccines
• immunotherapy
• neuro‐oncology

• Humans
• Glioma/immunology
• Glioma/therapy
• Cancer Vaccines/therapeutic use
• Cancer Vaccines/immunology
• Brain Neoplasms/immunology
• Brain Neoplasms/therapy
• Animals
• Immunotherapy/methods
• Immunotherapy/trends

• antigen loading
• dendritic cell vaccination
• glioblastoma
• immunotherapy
• positron emission tomography

• Adoptive immunotherapy
• Breast cancer
• Bryostatin 1
• Immunotherapy
• Ionomycin
• Melanoma
• Tumor-draining lymph nodes

• Humans
• Glioblastoma/therapy
• Oncolytic Viruses/genetics
• Brain Neoplasms/therapy
• Retrospective Studies
• Cancer Vaccines/therapeutic use
• Dendritic Cells/metabolism

• brain tumors
• cancer vaccines
• immune checkpoint inhibitors
• immune-oncology
• neuro-oncology
• pediatric neuro-oncology
• pediatric oncology
• radiation therapy

• Humans
• Child
• Central Nervous System Neoplasms/therapy
• Immunotherapy/adverse effects
• Radioimmunotherapy

• adoptive cell therapy
• clinical outcomes
• glioblastoma
• immunotherapy
• monoclonal antibodies
• oncolytic viruses
• systematic review
• target therapies
• vaccines

• Humans
• Glioblastoma/drug therapy
• Immune Checkpoint Inhibitors/pharmacology
• Cancer Vaccines/therapeutic use
• Cancer Vaccines/pharmacology
• Neoplasm Recurrence, Local/drug therapy
• Glioma/drug therapy
• Immunotherapy/methods
• Immunotherapy, Adoptive
• Brain Neoplasms/drug therapy
• Tumor Microenvironment

• Clinical trial
• control arm
• dc vaccine
• glioblastoma
• patient selection

• Humans
• Glioblastoma/drug therapy
• Cancer Vaccines/therapeutic use
• Dendritic Cells
• Glioma/drug therapy
• Brain Neoplasms/pathology
• Immunotherapy
• Tumor Microenvironment

• T32 GM007171 NIGMS NIH HHS

• dendritic cell
• dendritic cell vaccine
• glioma
• glioma microenvironment
• immunotherapy

• Humans
• Glioma
• Glioblastoma
• Brain Neoplasms
• Dendritic Cells
• Cancer Vaccines/therapeutic use
• Tumor Microenvironment

• DCVax®-L
• Glioblastoma
• dendritic cell vaccines (DC vaccines)
• external control arm (ECA)
• individualized multimodal immunotherapy (IMI)

• Humans
• Dendritic Cells
• Antigen Presentation
• T-Lymphocytes
• Glioma/therapy
• Immunotherapy
• Cancer Vaccines

• R37 CA258426 NCI NIH HHS
• P50 CA221747 NCI NIH HHS
• R35 CA197725 NCI NIH HHS
• R01 NS115955 NINDS NIH HHS

• CAR T Cell
• CNS
• glioma
• immune checkpoint inhibitor
• neurotoxicity
• oncolytic viruses
• primary brain tumor

Glioblastoma (GBM) stands out as the most common, aggressive form of primary malignant brain tumor conferring a devastatingly poor prognosis. Despite aggressive standard-of-care in surgical resection and chemoradiation with temozolomide, the median overall survival of patients still remains no longer than 15 months, due to significant tumor heterogeneity, immunosuppression induced by the tumor immune microenvironment and low mutational burden. Advances in immunotherapeutic approaches have revolutionized the treatment of various cancer types and become conceptually attractive for glioblastoma. In this review, we provide an overview of the basic knowledge underlying immune targeting and promising immunotherapeutic strategies including CAR T cells, oncolytic viruses, cancer vaccines, and checkpoint blockade inhibitors that have been recently investigated in glioblastoma. Current clinical trials and previous clinical trial findings are discussed, shedding light on novel strategies to overcome various limitations and challenges.

• Glioblastoma
• chimeric antigen receptor (CAR) T cell
• immunotherapy
• oncolytic virus

Glioblastoma remains a challenging disease to treat, despite well-established standard-of-care treatments, with a median survival consistently of less than 2 years. In this review, we delineate the unique disease-specific challenges for immunotherapies, both brain-related and non-brain-related, which will need to be adequately overcome for the development of effective treatments. We also review current immunotherapy treatments, with a focus on clinical applications, and propose future directions for the field of GBM immunotherapy.

• advanced MRI
• children
• conventional MRI
• diffusion-weighted imaging
• glioblastoma
• magnetic resonance spectroscopy
• perfusion weighted imaging

• Blood–brain barrier
• Brain
• Cancer
• Drug delivery
• Neural stem cells
• T cells

• Biological Transport/physiology
• Blood-Brain Barrier
• Brain
• Brain Diseases/therapy
• Drug Delivery Systems
• Humans

• R01 NS115971 NINDS NIH HHS
• R25 GM066534 NIGMS NIH HHS
• R37 CA222563 NCI NIH HHS

• brain tumor
• dendritic cells
• glioblastoma
• glioma
• immunotherapy
• review (article)
• vaccination

• CAR-T
• checkpoint inhibitors
• glioblastoma
• glioblastoma immunotherapy
• immunotherapy
• vaccine

• P50CA221747 NCI NIH HHS
• 1R37CA258426-01 National Cancer Research Institute
• N/A Neurosurgery Research and Education Foundation
• N/A Malnati's Brain Tumor Institute
• R37 CA258426 NCI NIH HHS

Glioblastoma (GB) is the most common high-grade intracranial malignant tumor with highly malignant biological behavior and a high recurrence rate. Although anti-PD-1/PD-L1 antibodies have achieved significant survival benefits in several kinds of solid tumors, the phase III clinical trial Checkmate 143 demonstrated that nivolumab, which targets PD-1, did not achieve survival benefits compared with bevacizumab in recurrent glioblastoma (rGB) patients. Nevertheless, neoadjuvant anti-PD-1 therapy followed by surgery and adjuvant anti-PD-1 therapy could effectively activate local and systemic immune responses and significantly improve the OS of rGB patients. Furthermore, several studies have also confirmed the progress made in applying tumor-specific peptide vaccination or chimeric antigen receptor-T (CAR-T) cell therapy to treat rGB patients, and successes with antibodies targeting other inhibitory checkpoints or costimulatory molecules have also been reported. These successes inspired us to explore candidate combination treatments based on anti-PD-1/PD-L1 antibodies. However, effective predictive biomarkers for clinical efficacy are urgently needed to avoid economic waste and treatment delay. Attempts to prolong the CAR-T cell lifespan and increase T cell infiltration through engineering techniques are addressing the challenge of strengthening T cell function. In this review, we describe the immunosuppressive molecular characteristics of rGB; clinical trials exploring anti-PD-1/PD-L1 therapy, tumor-specific peptide vaccination, and CAR-T cell therapy; candidate combination strategies; and issues related to strengthening T cell function.

• checkpoint inhibitors
• experimental therapeutics
• immunotherapy
• pediatric cancer
• vaccination

Although multiple meta-analyses on active specific immunotherapy treatment for glioblastoma multiforme (GBM) have demonstrated a significant prolongation of overall survival, no single research group has succeeded in demonstrating the efficacy of this type of treatment in a prospective, double-blind, placebo-controlled, randomized clinical trial. In this paper, we explain how the complexity of the tumor biology and tumor–host interactions make proper stratification of a control group impossible. The individualized characteristics of advanced therapy medicinal products for immunotherapy contribute to heterogeneity within an experimental group. The dynamics of each tumor and in each patient aggravate comparative stable patient groups. Finally, combinations of immunotherapy strategies should be integrated with first-line treatment. We illustrate the complexity of a combined first-line treatment with individualized multimodal immunotherapy in a group of 70 adults with GBM and demonstrate that the integration of immunogenic cell death treatment within maintenance chemotherapy followed by dendritic cell vaccines and maintenance immunotherapy might provide a step towards improving the overall survival rate of GBM patients.

Immunotherapies represent a promising strategy for glioblastoma multiforme (GBM) treatment. Different immunotherapies include the use of checkpoint inhibitors, adoptive cell therapies such as chimeric antigen receptor (CAR) T cells, and vaccines such as dendritic cell vaccines. Antibodies have also been used as toxin or radioactive particle delivery vehicles to eliminate target cells in the treatment of GBM. Oncolytic viral therapy and other immunogenic cell death-inducing treatments bridge the antitumor strategy with immunization and installation of immune control over the disease. These strategies should be included in the standard treatment protocol for GBM. Some immunotherapies are individualized in terms of the medicinal product, the immune target, and the immune tumor–host contact. Current individualized immunotherapy strategies focus on combinations of approaches. Standardization appears to be impossible in the face of complex controlled trial designs. To define appropriate control groups, stratification according to the Recursive Partitioning Analysis classification, MGMT promotor methylation, epigenetic GBM sub-typing, tumor microenvironment, systemic immune functioning before and after radiochemotherapy, and the need for/type of symptom-relieving drugs is required. Moreover, maintenance of a fixed treatment protocol for a dynamic, deadly cancer disease in a permanently changing tumor–host immune context might be inappropriate. This complexity is illustrated using our own data on individualized multimodal immunotherapies for GBM. Individualized medicines, including multimodal immunotherapies, are a rational and optimal yet also flexible approach to induce long-term tumor control. However, innovative methods are needed to assess the efficacy of complex individualized treatments and implement them more quickly into the general health system.

• GBM
• clinical trial
• dendritic cell vaccination
• individualized multimodal immunotherapy
• modulated electrohyperthermia
• newcastle disease virus

• biomarker
• children
• clinical trials
• drug development
• high-grade glioma
• pediatric

Dendritic cell-based and other vaccination strategies that use the patient’s own immune system for the treatment of cancer are gaining momentum. Most studies of therapeutic cancer vaccination have been performed in adults. However, since cancer is one of the leading causes of death among children past infancy in the Western world, the hope is that this form of active specific immunotherapy can play an important role in the pediatric population as well. Since children have more vigorous and adaptable immune systems than adults, therapeutic cancer vaccines are expected to have a better chance of creating protective immunity and preventing cancer recurrence in pediatric patients. Moreover, in contrast to conventional cancer treatments such as chemotherapy, therapeutic cancer vaccines are designed to specifically target tumor cells and not healthy cells or tissues. This reduces the likelihood of side effects, which is an important asset in this vulnerable patient population. In this review, we present an overview of the different therapeutic cancer vaccines that have been studied in the pediatric population, with a main focus on dendritic cell-based strategies. In addition, new approaches that are currently being investigated in clinical trials are discussed to provide guidance for further improvement and optimization of pediatric cancer vaccines.

• dendritic cells
• immunotherapy
• pediatric cancer
• tumor vaccination

Glioblastoma (GBM) is the most common and fatal primary central nervous system malignancy in adults with a median survival of less than 15 months. Surgery, radiation, and chemotherapy are the standard of care and provide modest benefits in survival, but tumor recurrence is inevitable. The poor prognosis of GBM has made the development of novel therapies targeting GBM of paramount importance. Immunotherapy via dendritic cells (DCs) has garnered attention and research as a potential strategy to boost anti-tumor immunity in recent years. As the “professional” antigen processing and presenting cells, DCs play a key role in the initiation of anti-tumor immune responses. Pre-clinical studies in GBM have shown long-term tumor survival and immunological memory in murine models with stimulation of DC activity with various antigens and costimulatory molecules. Phase I and II clinical trials of DC vaccines in GBM have demonstrated some efficacy in improving the median overall survival with minimal to no toxicity with promising initial results from the first Phase III trial. However, there remains no standardization of vaccines in terms of which antigens are used to pulse DCs ex vivo, sites of DC injection, and optimal adjuvant therapies. Future work with DC vaccines aims to elucidate the efficacy of DC-based therapy alone or in combination with other immunotherapy adjuvants in additional Phase III trials.

• checkpoint inhibition
• clinical trial
• combination therapy
• dendritic cells
• glioblastoma
• immunotherapy
• myeloid
• plasmacytoid
• vaccine

• Brain neoplasm
• Clinical trials
• Glioblastoma
• Immunotherapeutic
• Immunotherapy
• Vaccine

• Brain/immunology
• Brain Neoplasms/immunology
• Brain Neoplasms/mortality
• Brain Neoplasms/therapy
• Clinical Trials as Topic
• Glioblastoma/immunology
• Glioblastoma/mortality
• Glioblastoma/therapy
• Humans
• Immune Privilege/immunology
• Immune Tolerance/immunology
• Immunotherapy/methods
• Immunotherapy/trends
• Neoplastic Stem Cells/immunology
• Progression-Free Survival
• Tumor Microenvironment/immunology
• Vaccines/immunology
• Vaccines/therapeutic use

Glioblastoma (GBM) is the most common and fatal primary adult brain tumor. To date, various promising chemotherapeutic regimens have been trialed for use in GBM; however, temozolomide (TMZ) therapy remains the only US Food and Drug Administration-approved first-line chemotherapeutic option for newly diagnosed GBM. Despite maximal therapy with surgery and combined concurrent chemoradiation and adjuvant TMZ therapy, the median overall survival remains approximately 14 months. Given the failure of conventional chemotherapeutic strategies in GBM, there has been renewed interest in the role of immunotherapy in GBM. Dendritic cells are immune antigen-presenting cells that play a role in both the innate and adaptive immune system, thereby making them prime vehicles for immunotherapy via dendritic cell vaccinations (DCVs) in various cancers. There is great enthusiasm surrounding the use of DCVs for GBM with multiple ongoing trials. In this review, we comprehensively summarize the safety, efficacy, and quality of life results from 33 trials reporting on DCV for high-grade gliomas.

• dendritic cells
• glioblastoma
• glioma
• vaccine

Despite the combination of surgical resection, radio- and chemotherapy, median survival of glioblastoma multiforme (GBM) patients only slightly increased in the last years. Disease recurrence is definite with no effective therapy existing after tumor removal. Dendritic cell (DC) vaccination is a promising active immunotherapeutic approach. There is clear evidence that it is feasible, results in immunological anti-tumoral responses, and appears to be beneficial for survival and quality of life of GBM patients. Moreover, combining it with the standard therapy of GBM may allow exploiting synergies between the treatment modalities. In this randomized controlled trial, we seek to confirm these promising initial results.

One hundred and thirty-six newly diagnosed, isocitrate dehydrogenase wildtype GBM patients will be randomly allocated (1:1 ratio, stratified by O6-methylguanine-DNA-methyltransferase promotor methylation status) after near-complete resection in a multicenter, prospective phase II trial into two groups: (1) patients receiving the current therapeutic “gold standard” of radio/temozolomide chemotherapy and (2) patients receiving DC vaccination as an add-on to the standard therapy. A recruitment period of 30 months is anticipated; follow-up will be 2 years. The primary objective of the study is to compare overall survival (OS) between the two groups. Secondary objectives are comparing progression-free survival (PFS) and 6-, 12- and 24-month OS and PFS rates, the safety profile, overall and neurological performance and quality of life.

Until now, close to 500 GBM patients have been treated with DC vaccination in clinical trials or on a compassionate-use basis. Results have been encouraging, but cannot provide robust evidence of clinical efficacy because studies have been non-controlled or patient numbers have been low. Therefore, a prospective, randomized phase II trial with a sufficiently large number of patients is now mandatory for clear evidence regarding the impact of DC vaccination on PFS and OS in GBM.

Protocol code: GlioVax, date of registration: 17. February 2017.

Trial identifier: EudraCT-Number 2017–000304-14.

German Registry for Clinical Studies, ID: DRKS00013248 (approved primary register in the WHO network) and at ClinicalTrials.gov, ID: NCT03395587. Registered on 11 March 2017.

The online version of this article (10.1186/s13063-018-2659-7) contains supplementary material, which is available to authorized users.

• Dendritic cells
• Glioblastoma
• Immunotherapy
• Radiochemotherapy
• Vaccination

• Dendritic cell based vaccine
• Glioblastoma
• Immunotherapy
• Malignant glioma

• Animals
• Brain Neoplasms/immunology
• Brain Neoplasms/therapy
• Cancer Vaccines/therapeutic use
• Dendritic Cells/physiology
• Glioma/immunology
• Glioma/therapy
• Humans

• K08 NS092895 NINDS NIH HHS

• Dendritic cells
• Glioblastoma
• Glioma
• Rindopepimut
• Tumor vaccine

• Animals
• Brain Neoplasms/drug therapy
• Cancer Vaccines/therapeutic use
• Clinical Trials as Topic
• Glioblastoma/immunology
• Glioblastoma/therapy
• Glioma/immunology
• Glioma/therapy
• Humans
• Immunotherapy
• Treatment Outcome

• T32 CA196561 NCI NIH HHS

Purpose: The purpose of this paper is discriminating between tumor progression and response to treatment based on follow-up multi-parametric magnetic resonance imaging (MRI) data retrieved from glioblastoma multiforme (GBM) patients.

Materials and Methods: Multi-parametric MRI data consisting of conventional MRI (cMRI) and advanced MRI [i.e., perfusion weighted MRI (PWI) and diffusion kurtosis MRI (DKI)] were acquired from 29 GBM patients treated with adjuvant therapy after surgery. We propose an automatic pipeline for processing advanced MRI data and extracting intensity-based histogram features and 3-D texture features using manually and semi-manually delineated regions of interest (ROIs). Classifiers are trained using a leave-one-patient-out cross validation scheme on complete MRI data. Balanced accuracy rate (BAR)–values are computed and compared between different ROIs, MR modalities, and classifiers, using non-parametric multiple comparison tests.

Results: Maximum BAR–values using manual delineations are 0.956, 0.85, 0.879, and 0.932, for cMRI, PWI, DKI, and all three MRI modalities combined, respectively. Maximum BAR–values using semi-manual delineations are 0.932, 0.894, 0.885, and 0.947, for cMRI, PWI, DKI, and all three MR modalities combined, respectively. After statistical testing using Kruskal-Wallis and post-hoc Dunn-Šidák analysis we conclude that training a RUSBoost classifier on features extracted using semi-manual delineations on cMRI or on all MRI modalities combined performs best.

Conclusions: We present two main conclusions: (1) using T1 post-contrast (T1pc) features extracted from manual total delineations, AdaBoost achieves the highest BAR–value, 0.956; (2) using T1pc-average, T1pc-90th percentile, and Cerebral Blood Volume (CBV) 90th percentile extracted from semi-manually delineated contrast enhancing ROIs, SVM-rbf, and RUSBoost achieve BAR–values of 0.947 and 0.932, respectively. Our findings show that AdaBoost, SVM-rbf, and RUSBoost trained on T1pc and CBV features can differentiate progressive from responsive GBM patients with very high accuracy.

• boosting classifiers
• follow-up
• glioblastoma multiforme
• magnetic resonance imaging
• multi-parametric

• CD8(+) T cells
• GBM peptides
• IFN-γ
• cancer immunotherapy
• dextramer staining
• immune monitoring

• antitumor immunity
• dendritic cell vaccines
• immunogenic cell death
• immunogenicity
• immunotherapy
• tumor lysate

• Cancer stem-like cells
• Dendritic cells
• Glioblastoma
• Immunotherapy
• NIBIT 2014

• Dendritic Cells/immunology
• Glioblastoma/immunology
• Humans
• Immunotherapy/methods
• Stem Cells/immunology
• Stem Cells/pathology

• Associazione Italiana per la Ricerca sul Cancro
• Ministero della Salute

• Glioblastoma
• Glioma
• Immunomonitoring
• Immunotherapy
• Vaccine

• BBB, blood brain barrier
• CNS, central nervous system
• CTL, cytotoxic T-lymphocyte
• DC, dendritic cell
• DCVax®-L
• DTH, delayed tissue hypersensitivity
• EORTC, European Organization for Research and Treatment of Cancer
• FDA, Food and Drug Administration
• GBM, glioblastoma multiforme
• GM-CSF, granulocyte-macrophage colony-stimulating factor
• HGG, high-grade glioma
• IL-4, interleukin-4
• IMP, investigational medicinal product
• MHRA, Medicines and Healthcare products Regulatory Agency
• MRI, magnetic resonance imaging
• ND, newly diagnosed
• NIHR, National Institute for Health Research
• NWBT, Northwest Biotherapeutics Inc.
• OS, overall survival
• PEI, Paul-Ehrlich-Institute
• PFS, progression-free survival
• TAAs, tumor-associated antigens
• UCLA, University of California, Los Angeles, U.S.A., United States of America
• dendritic cells
• glioblastoma multiforme
• immunotherapy
• overall survival
• side effects
• vaccine

Dendritic cell (DC)-based immunotherapy has yielded promising results against high-grade glioma (HGG). However, the efficacy of DC vaccines is abated by HGG-induced immunosuppression and lack of attention toward the immunogenicity of the tumor lysate/cells used for pulsing DCs. A literature analysis of DC vaccination clinical trials in HGG patients delineated the following two most predominantly applied methods for tumor lysate preparation: freeze-thaw (FT)-induced necrosis or FT-necrosis followed by X-ray irradiation. However, from the available clinical evidence, it is unclear which of both methodologies has superior immunogenic potential. Using an orthotopic HGG murine model (GL261-C57BL/6), we observed that prophylactic vaccination with DCs pulsed with irradiated FT-necrotic cells (compared to FT-necrotic cells only) prolonged overall survival by increasing tumor rejection in glioma-challenged mice. This was associated, both in prophylactic and curative vaccination setups, with an increase in brain-infiltrating Th1 cells and cytotoxic T lymphocytes (CTL), paralleled by a reduced accumulation of regulatory T cells, tumor-associated macrophages (TAM) and myeloid-derived suppressor cells (MDSC). Further analysis showed that irradiation treatment of FT-necrotic cells considerably increased the levels of carbonylated proteins — a surrogate-marker of oxidation-associated molecular patterns (OAMPs). Through further application of antioxidants and hydrogen peroxide, we found a striking correlation between the amount of lysate-associated protein carbonylation/OAMPs and DC vaccine-mediated tumor rejection capacity thereby suggesting for the first time a role for protein carbonylation/OAMPs in at least partially mediating antitumor immunity. Together, these data strongly advocate the use of protein oxidation-inducing modalities like irradiation for increasing the immunogenicity of tumor lysate/cells used for pulsing DC vaccines.

• Antitumor immunity
• dendritic cell vaccination
• high-grade glioma
• oxidation-associated molecular patterns (OAMPs)
• protein carbonylation
• whole tumor lysate

Purpose. We have focused on finding a classifier that best discriminates between tumour progression and regression based on multiparametric MR data retrieved from follow-up GBM patients. Materials and Methods. Multiparametric MR data consisting of conventional and advanced MRI (perfusion, diffusion, and spectroscopy) were acquired from 29 GBM patients treated with adjuvant therapy after surgery over a period of several months. A 27-feature vector was built for each time point, although not all features could be obtained at all time points due to missing data or quality issues. We tested classifiers using LOPO method on complete and imputed data. We measure the performance by computing BER for each time point and wBER for all time points. Results. If we train random forests, LogitBoost, or RobustBoost on data with complete features, we can differentiate between tumour progression and regression with 100% accuracy, one time point (i.e., about 1 month) earlier than the date when doctors had put a label (progressive or responsive) according to established radiological criteria. We obtain the same result when training the same classifiers solely on complete perfusion data. Conclusions. Our findings suggest that ensemble classifiers (i.e., random forests and boost classifiers) show promising results in predicting tumour progression earlier than established radiological criteria and should be further investigated.

• Adoptive T cell therapy
• Medulloblastoma
• Pediatric brain tumors
• RNA-transfected dendritic cells

• Antigens, CD/metabolism
• Brain Neoplasms/drug therapy
• Brain Neoplasms/pathology
• Cell Separation
• Child
• Coculture Techniques
• Cytotoxicity Tests, Immunologic
• Dendritic Cells/drug effects
• Dendritic Cells/pathology
• Dendritic Cells/physiology
• Flow Cytometry
• Granulocyte Colony-Stimulating Factor/pharmacology
• Green Fluorescent Proteins/genetics
• Green Fluorescent Proteins/metabolism
• Humans
• Induction Chemotherapy
• Inhibitor of Apoptosis Proteins/genetics
• Inhibitor of Apoptosis Proteins/metabolism
• Leukapheresis
• Medulloblastoma/drug therapy
• Medulloblastoma/pathology
• Monocytes/cytology
• Monocytes/drug effects
• Monocytes/physiology
• Peptide Fragments/genetics
• Peptide Fragments/metabolism
• Phosphoproteins/genetics
• Phosphoproteins/metabolism
• Survivin
• Transduction, Genetic
• Viral Matrix Proteins/genetics
• Viral Matrix Proteins/metabolism

• DP2 CA174502 NCI NIH HHS
• P50 CA108786 NCI NIH HHS
• 5P50-CA108786 NCI NIH HHS

• Dendritic cells
• Glioblastoma
• Good Manufacturing Practices
• Immunotherapy
• Quality controls

• Antigens, Neoplasm/administration & dosage
• Antigens, Neoplasm/immunology
• Brain Neoplasms/therapy
• Cancer Vaccines/adverse effects
• Cancer Vaccines/immunology
• Cancer Vaccines/therapeutic use
• Cell Culture Techniques
• Cell Survival
• Clinical Trials, Phase I as Topic
• Cryopreservation
• Dendritic Cells/cytology
• Dendritic Cells/immunology
• Dendritic Cells/transplantation
• Glioblastoma/therapy
• Humans
• Immunotherapy/methods
• Limulus Test
• Lymphocyte Culture Test, Mixed
• Mycoplasma
• Quality Control
• Reproducibility of Results
• Translational Research, Biomedical/methods
• Vaccine Potency

High grade glioma is a rare brain cancer, incurable in spite of modern neurosurgery, radiotherapy, and chemotherapy. Novel approaches are in research, and immunotherapy emerges as a promising strategy. Clinical experiences with active specific immunotherapy demonstrate feasibility, safety and most importantly, but incompletely understood, prolonged long-term survival in a fraction of the patients. In relapsed patients, we developed an immunotherapy schedule and we categorized patients into clinically defined risk profiles. We learned how to combine immunotherapy with standard multimodal treatment strategies for newly diagnosed glioblastoma multiforme patients. The developmental program allows further improvements related to newest scientific insights. Finally, we developed a mode of care within academic centers to organize cell-based therapies for experimental clinical trials in a large number of patients.

• dendritic cell vaccines
• galectin-1
• immunomodulation
• immunotherapy
• malignant glioma
• oncolytic viruses

• Anaplastic glioma
• anti-angiogenic agents
• bevacizumab
• chemotherapy
• glioblastoma
• high grade glioma
• immunotherapy
• nitrosourea
• targeted therapy
• temozolomide

• dendritic cells
• glioblastoma multiforme
• high-grade glioma
• immunotherapy
• review

• glioblastoma
• immune checkpoint
• immunosuppression
• immunotherapy
• vaccine

• glioma
• dc vaccine
• cancer immunotherapy
• anti-tumor t cell
• sialylation

• Animals
• Antigens, CD/immunology
• Antigens, CD/metabolism
• Brain Neoplasms/immunology
• Brain Neoplasms/metabolism
• Brain Neoplasms/therapy
• CD8-Positive T-Lymphocytes/immunology
• CD8-Positive T-Lymphocytes/metabolism
• Cancer Vaccines/immunology
• Cancer Vaccines/pharmacology
• Dendritic Cells/immunology
• Female
• Glioblastoma/immunology
• Glioblastoma/metabolism
• Glioblastoma/therapy
• Glioma/immunology
• Glioma/metabolism
• Glioma/therapy
• Humans
• Immunotherapy, Adoptive/methods
• Integrin alpha Chains/immunology
• Integrin alpha Chains/metabolism
• Mice
• Mice, Inbred C57BL
• Neuraminidase/metabolism
• Neuraminidase/pharmacology
• Sialyltransferases/metabolism
• Sialyltransferases/pharmacology
• beta-Galactoside alpha-2,3-Sialyltransferase