Current Immunotherapeutic Approaches for Malignant Gliomas

Han, Myung‐Hoon; Kim, Choong Hyun

doi:10.14791/btrt.2022.10.e25

Cited by 5 publications

(3 citation statements)

References 134 publications

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“…Therefore, a vaccine composed of multiple antigenic peptides can ensure that a wide range of tumor-specific T-cell immune responses can be stimulated in the body, thereby avoiding the generation of tumor escape and preventing the immune attack on normal tissues. Personalized peptide vaccines are highly specific to individuals, and targeting neoantigens, can effectively stimulate immune response highly specific to cancer cells [41]. Furthermore, patients then receive clinical and immunological monitoring to determine the therapeutic effect and immunogenicity [42].…”

Section: Multi-target and Personalized Polypeptide Vaccinementioning

confidence: 99%

Peptide vaccine against glioblastoma: from bench to bedside

et al. 2022

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Glioblastoma accounts for almost half of all intracranial primary malignancies and has the worst prognosis. Because of its high malignancy and frequent recurrence after standard therapy, it is of great significance to explore new therapy options. Recently immune therapy has taken remarkable progress in a variety of tumors, among which peptide vaccines utilize peptide sequences based on tumor-specific antigens or tumor-associated antigen targets to activate self-immune response against tumor cells. However, due to the particularity of intracranial central nervous system tumors, the application of peptide vaccines in glioblastoma still faces challenges. This article mainly reviews the immune basis and important clinical trial results of peptide vaccine therapy for GBM, analyzes the reasons for its poor efficacy, and proposes the development direction of peptide vaccines for the unique challenges of immunotherapy in GBM. An in-depth understanding and elaboration of the application and related issues of peptide vaccine in the treatment of GBM will help to formulate relevant treatment strategies in future clinical and basic research.

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Section: Multi-target and Personalized Polypeptide Vaccinementioning

confidence: 99%

Peptide vaccine against glioblastoma: from bench to bedside

et al. 2022

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“…Cancer stemness is not only a fundamental process of tumor progression but also closely related to antigenicity, intratumoral heterogeneity, and immune suppression in cancer [ 3 ]. It is well-established that glioblastoma multiforme (GBM) cancer stem cells induce treatment resistance and an immunosuppressive GBM microenvironment [ 5 – 7 ]. The Wnt/β-catenin signaling pathway is known to play a crucial role in the progression of gliomas and maintenance of glioma stem cells by inhibiting tumor cell differentiation [ 8 – 10 ].…”

Section: Introductionmentioning

confidence: 99%

DKK3 expression is associated with immunosuppression and poor prognosis in glioblastoma, in contrast to lower-grade gliomas

et al. 2023

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Purpose We previously reported that expression of dickkopf-3 (DKK3), which is involved in the Wnt/β-catenin pathway, is significantly associated with prognosis in patients with glioblastoma multiforme (GBM). The aim of this study was to compare the association of DKK3 with other Wnt/β-catenin pathway-related genes and immune responses between lower grade glioma (LGG) and GBM. Methods We obtained the clinicopathological data of 515 patients with LGG (World Health Organization [WHO] grade II and III glioma) and 525 patients with GBM from the Cancer Genome Atlas (TCGA) database. We performed Pearson’s correlation analysis to investigate the relationships between Wnt/β-catenin-related gene expression in LGG and GBM. Linear regression analysis was performed to identify the association between DKK3 expression and immune cell fractions in all grade II to IV gliomas. Results A total of 1,040 patients with WHO grade II to IV gliomas were included in the study. As the grade of glioma increased, DKK3 showed a tendency to be more strongly positively correlated with the expression of other Wnt/β-catenin pathway-related genes. DKK3 was not associated with immunosuppression in LGG but was associated with downregulation of immune responses in GBM. We hypothesized that the role of DKK3 in the Wnt/β-catenin pathway might be different between LGG and GBM. Conclusion According to our findings, DKK3 expression had a weak effect on LGG but a significant effect on immunosuppression and poor prognosis in GBM. Therefore, DKK3 expression seems to play different roles, through the Wnt/β-catenin pathway, between LGG and GBM.

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“…Since GBM is the worst malignant tumor in the CNS, and it induces an immunosuppressive tumor microenvironment, there are high expectations for the efficacy of immunotherapy in the treatment of GBM. Therefore, extensive studies related to immunotherapy for GBM have been conducted, and many clinical trials are under way (23). Randomized clinical trials of immunotherapy in GBM are important for medical advances related to CNS malignant brain tumors.…”

Section: Introductionmentioning

confidence: 99%

Efficacy of Cytokine-Induced Killer Cell Immunotherapy for Patients With Pathologically Pure Glioblastoma

et al. 2022

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The most common malignant central nervous system tumor is glioblastoma multiforme (GBM). Cytokine-induced killer (CIK) cell therapy is a promising type of adoptive cell immunotherapy for various cancers. We previously conducted a randomized clinical trial on CIK cell therapy in patients with GBM. The aim of this study was to evaluate the efficacy of CIK immunotherapy for patients with pathologically pure GBM, using data from our previous randomized clinical trial. The difference between overall survival (OS) and progression-free survival (PFS) according to CIK immunotherapy was analyzed using the Kaplan–Meier method. Hazard ratios were calculated using univariate and multivariate Cox regression analyses to determine whether CIK cell immunotherapy was independently associated with higher OS and PFS in patients with pure GBM. A total of 156 eligible patients were included in the modified intention-to-treat (mITT) population. We confirmed that 125 (80.1%) GBM samples were pure GBM tumors without the presence of other types of tumors. For patients with pure GBM, Kaplan-Meier analysis showed no significant difference in OS between the CIK cell treatment and control groups. However, multivariate Cox regression demonstrated CIK cell immunotherapy as an independent predictor of greater OS (hazard ratio, 0.59; 95% CI, 0.36–0.97; p = 0.038) and PFS (hazard ratio, 0.55; 95% CI, 0.36–0.84; p = 0.001) in patients with pathologically pure GBM in the mITT population. This study showed that CIK cell immunotherapy combined with conventional temozolomide chemoradiotherapy could prolong OS and PFS in patients with newly diagnosed pathologically pure GBM, with no significant adverse events related to treatment. However, unlike the results of multivariate Cox analysis, no statistical significance of CIK cell immunotherapy in OS in Kaplan-Meier analysis raises a question. Further studies are required to validate these results.

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Current Immunotherapeutic Approaches for Malignant Gliomas

Cited by 5 publications

References 134 publications

Peptide vaccine against glioblastoma: from bench to bedside

Peptide vaccine against glioblastoma: from bench to bedside

DKK3 expression is associated with immunosuppression and poor prognosis in glioblastoma, in contrast to lower-grade gliomas

Efficacy of Cytokine-Induced Killer Cell Immunotherapy for Patients With Pathologically Pure Glioblastoma

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