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Review
. 2022 Nov 22:13:1038096.
doi: 10.3389/fimmu.2022.1038096. eCollection 2022.

Pediatric versus adult high grade glioma: Immunotherapeutic and genomic considerations

Affiliations
Review

Pediatric versus adult high grade glioma: Immunotherapeutic and genomic considerations

Payal Aggarwal et al. Front Immunol. .

Abstract

High grade gliomas are identified as malignant central nervous tumors that spread rapidly and have a universally poor prognosis. Historically high grade gliomas in the pediatric population have been treated similarly to adult high grade gliomas. For the first time, the most recent classification of central nervous system tumors by World Health Organization has divided adult from pediatric type diffuse high grade gliomas, underscoring the biologic differences between these tumors in different age groups. The objective of our review is to compare high grade gliomas in the adult versus pediatric patient populations, highlighting similarities and differences in epidemiology, etiology, pathogenesis and therapeutic approaches. High grade gliomas in adults versus children have varying clinical presentations, molecular biology background, and response to chemotherapy, as well as unique molecular targets. However, increasing evidence show that they both respond to recently developed immunotherapies. This review summarizes the distinctions and commonalities between the two in disease pathogenesis and response to therapeutic interventions with a focus on immunotherapy.

Keywords: adult; glioblastoma; high grade glioma; immunotherapy; pediatric.

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Conflict of interest statement

MC serves as a consultant for Jazz, Omeros, Astra Zeneca, Nektar Therapeutics and Novartis and a member of the Speakers Bureau for Jazz, Servier, Amgen, Sanofi and Sobi. DL reports personal fees and other from Kiadis Pharma, CytoSen Therapeutics, Courier Therapeutics, and Caribou Biosciences outside the submitted work; In addition, DL has a patent broadly related to NK cell therapy of cancer with royalties paid to Kiadis Pharma. TC recently served as a one-time consultant to Blueprint, Incyte, Oncopeptides, serves as a DSMB chair for SpringWorks and is a cofounder of Vironexis Biotherapeutics, Inc. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
For the Rindopepimut vaccine, EGFRvIII specific peptide is introduced into the bloodstream and the peptide is processed and presented by the APC causing the activation of CD4 helper T cells and CD8+ cytotoxic T cells. The cytotoxic T-cells are then able to cause lysis of the glioma tumor cells.
Figure 2
Figure 2
Dendritic cells are isolated from the patient’s blood, allowed to mature and then tumor lysate is loaded into the dendritic cells and given back to the patient as a vaccine.
Figure 3
Figure 3
Anti-GD2 immunotherapy of glioblastoma cells based on the innate immune system. In the presence of anti-GD2 monoclonal antibodies,GBM cells would be susceptible to the activity of natural killer (NK) cells that would mediate antibody-dependent cell mediated cytotoxicity (ADCC), granulocyte mediated ADCC, and monocyte macrophage ADCC.
Figure 4
Figure 4
Four patients with the diagnosis of diffuse intrinsic pontine glioma were enrolled in the phase 1 clinical trial of GD2-CAR T cells. Each patient received GD2 CAR T cells. These CAR T cells were generated by isolating the patient’s T-cells from the rest of the blood, inserting GD2 CAR mRNA and administering the GD2 CAR T cells back to the patients. Expansion of CAR T cells, increased inflammation after treatment and increased CAR T cells in the CSF during peak inflammation was observed.

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