Cytokines associated with toxicity in the treatment of recurrent glioblastoma with aflibercept

Shonka, Nicole; Piao, Yuji; Gilbert, Mark R.; Yung, W. K. Alfred; Chang, Susan M.; DeAngelis, Lisa M.; Lassman, Andrew B.; Li, Jun; Cloughesy, Timothy F.; Robins, H. Ian; Lloyd, Rita; Chen, Alice; Prados, Michael D.; Wen, Patrick Y.; Heymach, John V.; Groot, John F. de

doi:10.1007/s11523-013-0254-0

Cited by 8 publications

(5 citation statements)

References 31 publications

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“…Less is known about the role of IL-13 in glioblastoma biology. A recent clinical study demonstrated that changes in plasma IL-13 levels, during patient treatment with a novel anti-angiogenic agent, were associated with increased on-target toxicities [ 18 ].…”

Section: Discussionmentioning

confidence: 99%

Stable luciferase expression does not alter immunologic or in vivo growth properties of GL261 murine glioma cells

Clark

Safaee

et al. 2014

J Transl Med

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BackgroundGL261 cells are murine glioma cells that demonstrate proliferation, invasion, and angiogenesis when implanted in syngeneic C57BL/6 mice, providing a highly useful immunocompetent animal model of glioblastoma. Modification of tumor cells for luciferase expression enables non-invasive monitoring of orthotopic tumor growth, and has proven useful for studying glioblastoma response to novel therapeutics. However, tumor modification for luciferase has the potential for evoking host immune response against otherwise syngeneic tumor cells, thereby mitigating the tumor cells’ value for tumor immunology and immunotherapy studies.MethodsGL261 cells were infected with lentivirus containing a gene encoding firefly luciferase (GL261.luc). In vitro proliferation of parental (unmodified) GL261 and GL261.luc was measured on days 0, 1, 2, 4, and 7 following plating, and the expression of 82 mouse cytokines and chemokines were analyzed by RT-PCR array. Cell lines were also evaluated for differences in invasion and migration in modified Boyden chambers. GL261 and GL261.luc cells were then implanted intracranially in C57BL/6 mice, with GL261.luc tumor growth monitored by quantitative bioluminescence imaging, and all mice were followed for survival to compare relative malignancy of tumor cells.ResultsNo difference in proliferation was indicated for GL261 vs. GL261.luc cells (p>0.05). Of the 82 genes examined by RT-PCR array, seven (9%) exhibited statistically significant change after luciferase modification. Of these, only three changed by greater than 2-fold: BMP-2, IL-13, and TGF-β2. No difference in invasion (p=0.67) or migration (p=0.26) was evident between modified vs. unmodified cells. GL261.luc cell luminescence was detectable in the brains of C57BL/6 mice at day 5 post-implantation, and tumor bioluminescence increased exponentially to day 19. Median overall survival was 20.2 days versus 19.7 days for mice receiving implantation with GL261 and GL261.luc, respectively (p=0.62). Histopathologic analysis revealed no morphological difference between tumors, and immunohistochemical analysis showed no significant difference for staining of CD3, Ki67, or CD31 (p>0.05 for all).ConclusionsLuciferase expression in GL261 murine glioma cells does not affect GL261 proliferation, invasion, cytokine expression, or in vivo growth. Luciferase modification increases their utility for studying tumor immunology and immunotherapeutic approaches for treating glioblastoma.

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Section: Discussionmentioning

confidence: 99%

Stable luciferase expression does not alter immunologic or in vivo growth properties of GL261 murine glioma cells

Clark

Safaee

et al. 2014

J Transl Med

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“…In one study, plasma profiling of patients treated with the antiangiogenic agent aflibercept in 28 patients with recurrent GBM revealed that changes in IL-13 from baseline to 24 h predicted on-target toxicities. Increases in IL-1β, IL-6, and IL-10 at 24 h were significantly associated with fatigue [142].…”

Section: Cytokines Associated With Toxicity In Glioma Patientsmentioning

confidence: 90%

The Use of Targeted Cytokines as Cancer Therapeutics in Glioblastoma

Sooreshjani

Tripathi

Dussold

et al. 2023

Cancers

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Cytokines play an important role in regulating the immune response. Although there is great interest in exploiting cytokines for cancer immunotherapy, their clinical potential is limited by their pleiotropic properties and instability. A variety of cancer cell-intrinsic and extrinsic characteristics pose a barrier to effective treatments including cytokines. Recent studies using gene and cell therapy offer new opportunities for targeting cytokines or their receptors, demonstrating that they are actionable targets. Current efforts such as virotherapy, systemic cytokine therapy, and cellular and gene therapy have provided novel strategies that incorporate cytokines as potential therapeutic strategies for glioblastoma. Ongoing research on characterizing the tumor microenvironment will be informative for prioritization and combinatorial strategies of cytokines for future clinical trials. Unique therapeutic opportunities exist at the convergence of cytokines that play a dual role in tumorigenesis and immune modulation. Here, we discuss the underlying strategies in pre- and clinical trials aiming to enhance treatment outcomes in glioblastoma patients.

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“…They can generate cytokines including interleukin-10 (IL-10) and transforming growth factor-beta (TGF-β), which suppress the activity of immune cells like T-cells and NK cells while promoting GB development and invasion (Garg et al, 2017;Jiao et al, 2017). Furthermore, B cells can secrete pro-angiogenic factors such as VEGF, CXC chemokine ligand 12 (CXCL12), and CXC chemokine ligand 13 (CXCL13), which stimulate the formation of new blood vessels, provide nutrients and oxygen to the tumor, and promote GB growth and invasion (Shonka et al, 2013).…”

Section: B Cellsmentioning

confidence: 99%

Insights into the glioblastoma tumor microenvironment: current and emerging therapeutic approaches

Tripathy,

Panda,

Biswal

et al. 2024

Front. Pharmacol.

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Glioblastoma (GB) is an intrusive and recurrent primary brain tumor with low survivability. The heterogeneity of the tumor microenvironment plays a crucial role in the stemness and proliferation of GB. The tumor microenvironment induces tumor heterogeneity of cancer cells by facilitating clonal evolution and promoting multidrug resistance, leading to cancer cell progression and metastasis. It also plays an important role in angiogenesis to nourish the hypoxic tumor environment. There is a strong interaction of neoplastic cells with their surrounding microenvironment that comprise several immune and non-immune cellular components. The tumor microenvironment is a complex network of immune components like microglia, macrophages, T cells, B cells, natural killer (NK) cells, dendritic cells and myeloid-derived suppressor cells, and non-immune components such as extracellular matrix, endothelial cells, astrocytes and neurons. The prognosis of GB is thus challenging, making it a difficult target for therapeutic interventions. The current therapeutic approaches target these regulators of tumor micro-environment through both generalized and personalized approaches. The review provides a summary of important milestones in GB research, factors regulating tumor microenvironment and promoting angiogenesis and potential therapeutic agents widely used for the treatment of GB patients.

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Cytokines associated with toxicity in the treatment of recurrent glioblastoma with aflibercept

Cited by 8 publications

References 31 publications

Stable luciferase expression does not alter immunologic or in vivo growth properties of GL261 murine glioma cells

Stable luciferase expression does not alter immunologic or in vivo growth properties of GL261 murine glioma cells

The Use of Targeted Cytokines as Cancer Therapeutics in Glioblastoma

Insights into the glioblastoma tumor microenvironment: current and emerging therapeutic approaches

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