A systematic review on poly(I:C) and poly-ICLC in glioblastoma: adjuvants coordinating the unlocking of immunotherapy

Waele, Jorrit De; Verhezen, Tias; Heijden, Sanne van der; Berneman, Zwi; Peeters, Marc; Lardon, Filip; Wouters, An; Smits, Evelien

doi:10.1186/s13046-021-02017-2

Cited by 54 publications

(33 citation statements)

References 109 publications

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“…Glioblastoma (World Health Organization grade IV), the most malignant form of intracranial tumor found in adults, accounting for 54% of all gliomas, is incurable due to its high proliferation ability, high invasiveness, resistance to various therapies, and high rate of postoperative recurrence ( 1 ). Despite improvements in patients outcomes with the combined radiotherapy and temozolomide regimen since 2005, the median survival duration after the initial diagnosis remains at 15 months with a 5-year survival rate of 7.2% ( 2 ). Thus, effective therapeutic approaches for patients with GBM are urgently needed.…”

Section: Introductionmentioning

confidence: 99%

RRM2 Mediates the Anti-Tumor Effect of the Natural Product Pectolinarigenin on Glioblastoma Through Promoting CDK1 Protein Degradation by Increasing Autophagic Flux

et al. 2022

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The natural product pectolinarigenin exerts anti-inflammatory activity and anti-tumor effects, and exhibits different biological functions, particularly in autophagy and cell cycle regulation. However, the antineoplastic effect of pectolinarigenin on glioblastoma (GBM) remains unclear. In the present study, we found that pectolinarigenin inhibits glioblastoma proliferation, increases autophagic flux, and induces cell cycle arrest by inhibiting ribonucleotide reductase subunit M2 (RRM2), which can be reversed by RRM2 overexpression plasmid. Additionally, pectolinarigenin promoted RRM2 protein degradation via autolysosome-dependent pathway by increasing autophagic flow. RRM2 knockdown promoted the degradation of CDK1 protein through autolysosome-dependent pathway by increasing autophagic flow, thereby inhibiting the proliferation of glioblastoma by inducing G2/M phase cell cycle arrest. Clinical data analysis revealed that RRM2 expression in glioma patients was inversely correlated with the overall survival. Collectively, pectolinarigenin promoted the degradation of CDK1 protein dependent on autolysosomal pathway through increasing autophagic flux by inhibiting RRM2, thereby inhibiting the proliferation of glioblastoma cells by inducing G2/M phase cell cycle arrest, and RRM2 may be a potential therapeutic target and a prognosis and predictive biomarker in GBM patients.

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Section: Introductionmentioning

confidence: 99%

RRM2 Mediates the Anti-Tumor Effect of the Natural Product Pectolinarigenin on Glioblastoma Through Promoting CDK1 Protein Degradation by Increasing Autophagic Flux

et al. 2022

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“…Also, while CpG is an effective adjuvant in mice due to the promiscuous nature of TLR9 expression in murine B cells and T cells, its effect is limited in humans ( 71 ). Future translational studies may consider poly(I:C) (polyinosinic-polycytidylic acid) as an alternative adjuvant choice ( 72 ). Despite these limitations, the nanofiber vaccine illustrates a supramolecular strategy to leverage vaccine-induced humoral responses, in combination with CD8 + T cell responses, for improved cancer treatment.…”

Section: Discussionmentioning

confidence: 99%

Multiepitope supramolecular peptide nanofibers eliciting coordinated humoral and cellular antitumor immune responses

Wen

Bernstein

et al. 2022

Sci. Adv.

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Subunit vaccines inducing antibodies against tumor-specific antigens have yet to be clinically successful. Here, we use a supramolecular α-helical peptide nanofiber approach to design epitope-specific vaccines raising simultaneous B cell, CD8 + T cell, and CD4 + T cell responses against combinations of selected epitopes and show that the concurrent induction of these responses generates strong antitumor effects in mice, with significant improvements over antibody or CD8 + T cell–based vaccines alone, in both prophylactic and therapeutic subcutaneous melanoma models. Nanofiber vaccine–induced antibodies mediated in vitro tumoricidal antibody-dependent cellular cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis (ADCP). The addition of immune checkpoint and phagocytosis checkpoint blockade antibodies further improved the therapeutic effect of the nanofiber vaccines against murine melanoma. These findings highlight the potential clinical benefit of vaccine-induced antibody responses for tumor treatments, provided that they are accompanied by simultaneous CD8 + and CD4 + responses, and they illustrate a multiepitope cancer vaccine design approach using supramolecular nanomaterials.

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“…For the fibroblast cells used, IFNβ would be anticipated to be the primary IFN produced in response to dsRNA (Li et al, 2018). However, in glioblastoma cells, variations in IFN competence have been reported (Dick and Hubbell, 1987;Imaizumi et al, 2014;De Waele et al, 2021). When previously explored in multiple glioblastoma cell lines, pIC was shown to modestly induce IFNβ expression but significantly induced ISG (ISG15 and CXCL10) expression in some of these cultures (Wollmann et al, 2007).…”

Section: Discussionmentioning

confidence: 99%

Long dsRNA mediated RNA interference (dsRNAi) is antiviral in interferon competent mammalian cells

Semple

Jacob

Mossman

et al. 2022

Preprint

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In invertebrate cells, RNA interference (RNAi) acts as a powerful defense against virus infection by cleaving virally produced long dsRNA into siRNA by Dicer and loaded into RISC which can then destroy/disrupt complementary viral mRNA sequences. Comparatively in mammalian cells, the type I interferon (IFN) pathway is the cornerstone of the innate antiviral response. Although the cellular machinery for RNAi functions in mammalian cells, its role in the antiviral response remains controversial. Here we show that IFN competent mammalian cells engage in dsRNA-mediated RNAi. We found that pre-soaking mammalian cells with concentrations of sequence-specific dsRNA too low to induce IFN production could significantly inhibit viral replication, including SARS-CoV-2. This phenomenon was dependent on dsRNA length, was comparable in effect to transfected siRNAs, and could knockdown multiple sequences at once. Additionally, Dicer-knockout cell lines were incapable of this inhibition, confirming use of RNAi. This represents the first evidence that soaking with gene-specific dsRNA can generate viral knockdown in mammalian cells. Furthermore, demonstrating RNAi below the threshold of IFN induction has uses as a novel therapeutic platform.

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A systematic review on poly(I:C) and poly-ICLC in glioblastoma: adjuvants coordinating the unlocking of immunotherapy

Cited by 54 publications

References 109 publications

RRM2 Mediates the Anti-Tumor Effect of the Natural Product Pectolinarigenin on Glioblastoma Through Promoting CDK1 Protein Degradation by Increasing Autophagic Flux

RRM2 Mediates the Anti-Tumor Effect of the Natural Product Pectolinarigenin on Glioblastoma Through Promoting CDK1 Protein Degradation by Increasing Autophagic Flux

Multiepitope supramolecular peptide nanofibers eliciting coordinated humoral and cellular antitumor immune responses

Long dsRNA mediated RNA interference (dsRNAi) is antiviral in interferon competent mammalian cells

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