Dendritic cell vaccination for glioblastoma multiforme patients: has a new milestone been reached?
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ABSTRACT:
SUBMITTER: Van Gool SW
PROVIDER: S-EPMC10493805 | biostudies-literature | 2023 Aug
REPOSITORIES: biostudies-literature
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Dendritic cell vaccination for glioblastoma multiforme patients: has a new milestone been reached?
Van Gool Stefaan W SW Makalowski Jennifer J Kampers Linde F C LFC Van de Vliet Peter P Sprenger Tobias T Schirrmacher Volker V Stücker Wilfried W
Translational cancer research 20230728 8
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Project description:Human Glioblastoma Multiforme tumors taken before dendritic cell vaccination, the recurrent tumors taken after vaccination and control GBM tumors from non vaccinated patients. Keywords: Disease State Analysis
2009-04-03 | GSE11100 | GEO
Project description:BackgroundGlioblastoma (GBM) is the most common and lethal primary malignant glioma in adults. Dendritic cell (DC) vaccines have demonstrated promising results in GBM clinical trials. However, some patients do not respond well to DC therapy, with survival rates similar to those of conventional therapy. We retrospectively analyzed clinical and laboratory data to evaluate the factors affecting vaccine treatment.MethodsForty-seven patients with de novo GBM were enrolled at China Medical University Hospital between 2005 and 2010 and divided into two subgroups. One subgroup of 27 patients received postsurgical adjuvant immunotherapy with autologous dendritic cell/tumor antigen vaccine (ADCTA) in conjunction with conventional treatment of concomitant chemoradiotherapy (CCRT) with temozolomide. The other 20 patients received only postsurgical conventional treatment without immunotherapy. Immunohistochemistry for CD45, CD4, CD8, programed death ligand 1 (PD-L1), and programed death 1 (PD-1) was performed on sections of surgical tumor specimens and peripheral blood mononuclear cells (PBMCs). Pearson's correlation, Cox proportional hazard model, and Kaplan-Meier analyses were performed to examine the correlations between the prognostic factors and survival rates.ResultsYounger age (<57 years), gross total resection, and CCRT and PD-1+ lymphocyte counts were significant prognostic factors of overall survival (OS) and progression-free survival (PFS) in the ADCTA group. Sex, CD45+ lymphocyte count, CD4+ or CD8+ lymphocyte count, tumor PD-L1 expression, isocitrate dehydrogenase 1 mutation, and O6 methylguanine-DNA methyltransferase promoter methylation status were not significant factors in both groups. In the ADCTA group, patients with tumor-infiltrating lymphocytes (TILs) with a lower PD-1+/CD8+ ratio (≤0.21) had longer OS and PFS (median OS 60.97 months, P < 0.001 and PFS 11.2 months, P < 0.008) compared to those with higher PD-1+/CD8+ ratio (>0.21) (median OS 20.07 months, P < 0.001 and PFS 4.43 months, P < 0.008). Similar results were observed in patients' PBMCs; lymphocyte counts with lower PD-1+/CD8+ ratio (≤0.197) had longer OS and PFS. There was a significant correlation of PD-1+/CD8+ ratio between TILs and PBMCs (Pearson's correlation R2 = 0.6002, P < 0.001). By contrast, CD4-, CD8-, but PD-1+, CD45+ tumor-infiltrating lymphocytes have no impact on OS and PFS (P = 0.073 and P = 0.249, respectively).ConclusionFor patients receiving DC vaccine adjuvant therapy, better outcomes are predicted in patients with younger age, with TILs or PBMCs with lower PD-1+/CD8+ ratio, with gross tumor resection, and receiving CCRT.
| S-EPMC5992384 | biostudies-literature
Project description:Human Glioblastoma Multiforme tumors taken before dendritic cell vaccination, the recurrent tumors taken after vaccination and control GBM tumors from non vaccinated patients. Experiment Overall Design: Six Glioblastoma Multiforme patients underwent surgery. Their brain tumors were removed and analyzed via microarray. The lysate from the tumors were cultured with the patients' dendritic cells and the DCs were injected back into the patients. The patients GBMs returned and they underwent surgery a second time and those tumors were also analyzed via microarray. Tumors from the first and second GBM surgeries of 5 patients who did not receive DC vaccines are included as controls.
2009-04-11 | E-GEOD-11100 | biostudies-arrayexpress
Project description:IntroductionGlioblastoma is the most common primary brain tumor in adults and prognosis remains poor with a median survival of approximately 15-17 months. This review provides an overview of recent advances in the field of glioblastoma immunotherapy. Areas covered: Recent advances in dendritic cell vaccination immunotherapy are showing encouraging results in clinical trials and promise to extend patient survival. In this report we discuss current scientific knowledge regarding dendritic cell (DC) vaccines, including approaches to differentiating, priming, and injecting dendritic cells to achieve maximal anti-tumor efficacy in glioblastoma. These findings are compared to recently completed and currently ongoing glioblastoma clinical trials. Novel methods such as 'fastDCs' and vaccines targeting DCs in-vivo may offer more effective treatment when compared to traditional DC vaccines and have already entered the clinic. Expert commentary: Finally, we discuss the challenges of T-cell dysfunctions caused by glioblastoma immunosuppression and how they affect dendritic cell vaccinations approaches.
| S-EPMC5479410 | biostudies-literature
Project description:Human Glioblastoma Multiforme tumors taken before dendritic cell vaccination, the recurrent tumors taken after vaccination and control GBM tumors from non vaccinated patients. Experiment Overall Design: Six Glioblastoma Multiforme patients underwent surgery. Their brain tumors were removed and analyzed via microarray. The lysate from the tumors were cultured with the patients' dendritic cells and the DCs were injected back into the patients. The patients GBMs returned and they underwent surgery a second time and those tumors were also analyzed via microarray. Tumors from the first and second GBM surgeries of 5 patients who did not receive DC vaccines are included as controls.
| S-ECPF-GEOD-11100 | biostudies-other
Project description:Cell therapies, including tumor antigen-loaded dendritic cells used as therapeutic cancer vaccines, offer treatment options for patients with malignancies. We evaluated the feasibility, safety, immunogenicity, and clinical activity of adjuvant vaccination with Wilms' tumor protein (WT1) mRNA-electroporated autologous dendritic cells (WT1-mRNA/DC) in a single-arm phase I/II clinical study of patients with advanced solid tumors receiving standard therapy. Disease status and immune reactivity were evaluated after 8 weeks and 6 months. WT1-mRNA/DC vaccination was feasible in all patients, except one. Vaccination was well tolerated without evidence of systemic toxicity. The disease control rate and overall response rate among a total of 39 evaluable patients were 74.4% and 12.8%, respectively. Median overall survival (OS) was 43.7 months among 13 patients with glioblastoma multiforme, 41.9 months among 12 patients with metastatic breast cancer, and 48.8 months among 10 patients with malignant pleural mesothelioma, comparing favourably with historical controls reported in the literature. OS was longer in patients with stable disease at 8 weeks and disease control at 6 months versus patients without disease control at either time point. Disease control and higher OS were associated with antigen-specific type 1 CD4+ and/or CD8+ T-lymphocyte responses, mainly induced by WT1-mRNA/DC vaccination. Antigen-nonspecific type 2 CD8+ T-cell responses were common before WT1-mRNA/DC vaccination but did not show any association with clinical outcome. Collectively, these data indicate that WT1-mRNA/DC vaccination is feasible, safe, and immunogenic and shows clinical activity in patients with advanced solid tumors, suggesting that it has the potential to help improve their survival.
| S-EPMC11755790 | biostudies-literature
Project description:Glioblastoma multiforme (GBM) is the most aggressive and lethal primary glial brain tumor. It has an unfavorable prognosis and relatively ineffective treatment protocols, with the median survival of patients being ~15 months. Tumor resistance to treatment is associated with its cancer stem cells (CSCs). At present, there is no medication or technologies that have the ability to completely eradicate CSCs, and immunotherapy (IT) is only able to prolong the patient's life. The present review aimed to investigate systemic solutions for issues associated with immunosuppression, such as ineffective IT and the creation of optimal conditions for CSCs to fulfill their lethal potential. The present review also investigated the main methods involved in local immunosuppression treatment, and highlighted the associated disadvantages. In addition, novel treatment options and targets for the elimination and regulation of CSCs with adaptive and active IT are discussed. Antagonists of TGF-β inhibitors, immune checkpoints and other targeted medication are also summarized. The role of normal hematopoietic stem cells (HSCs) in the mechanisms underlying systemic immune suppression development in cases of GBM is analyzed, and the potential reprogramming of HSCs during their interaction with cancer cells is discussed. Moreover, the present review emphasizes the importance of the aforementioned interactions in the development of immune tolerance and the inactivation of the immune system in neoplastic processes. The possibility of solving the problem of systemic immunosuppression during transplantation of donor HSCs is discussed.
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Project description:Peroxisome proliferator-activated receptor ? coactivator 1? (PGC1?) is a key modulator of mitochondrial biogenesis. It is a coactivator of multiple transcription factors and regulates metabolic processes. However, little is known about the expression and function of PGC1? in glioblastoma multiforme (GBM), the most prevalent and invasive type of brain tumor. The purpose of the present study was to investigate the biological function, localization and expression of PGC1? in GBM. It was observed that PGC1? expression is increased in the tumor cells, and a higher level of expression was observed in the mitochondria. Bioinformatics analyses identified that metabolic and mitochondrial genes were highly expressed in GBM cells, with a high PGC1? mRNA expression. Notably, mitochondrial function-associated genes were highly expressed in cells alongside high PGC1? expression. Collectively, the results of the present study indicate that PGC1? is associated with mitochondrial dysfunction in GBM and may have a role in tumor pathogenesis and progression.
| S-EPMC5453058 | biostudies-literature
Project description:Glioblastoma multiforme (GBM) is the most common primary brain tumour in adults. The standard therapy for GBM is maximal surgical resection followed by radiotherapy with concurrent and adjuvant temozolomide (TMZ). In spite of the extensive treatment, the disease is associated with poor clinical outcome. Further intensification of the standard treatment is limited by the infiltrating growth of the GBM in normal brain areas, the expected neurological toxicities with radiation doses >60 Gy and the dose-limiting toxicities induced by systemic therapy. To improve the outcome of patients with GBM, alternative treatment modalities which add low or no additional toxicities to the standard treatment are needed. Many Phase II trials on new chemotherapeutics or targeted drugs have indicated potential efficacy but failed to improve the overall or progression-free survival in Phase III clinical trials. In this review, we will discuss contemporary issues related to recent technical developments and new metabolic strategies for patients with GBM including MR (spectroscopy) imaging, (amino acid) positron emission tomography (PET), amino acid PET, surgery, radiogenomics, particle therapy, radioimmunotherapy and diets.
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Project description:The most lethal form of brain cancer, glioblastoma multiforme, is characterized by rapid growth and invasion facilitated by cell migration and degradation of the extracellular matrix. Despite technological advances in surgery and radio-chemotherapy, glioblastoma remains largely resistant to treatment. New approaches to study glioblastoma and to design optimized therapies are greatly needed. One such approach harnesses computational modeling to support the design and delivery of glioblastoma treatment. In this paper, we critically summarize current glioblastoma therapy, with a focus on emerging nanomedicine and therapies that capitalize on cell-specific signaling in glioblastoma. We follow this summary by discussing computational modeling approaches focused on optimizing these emerging nanotherapeutics for brain cancer. We conclude by illustrating how mathematical analysis can be used to compare the delivery of a high potential anticancer molecule, delphinidin, in both free and nanoparticle loaded forms across the blood-brain barrier for glioblastoma.
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