Exploring the antitumor effect of virus in malignant glioma

Saha, Dipongkor; Ahmed, Seemin Seher; Rabkin, Samuel D.

doi:10.1358/dof.2015.040.11.2383070

Cited by 25 publications

(15 citation statements)

References 139 publications

(205 reference statements)

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“…Therefore, mutation in the ICP6 gene makes viral infection and replication tumor-specific and thereby increases safety. Similar to ICP6 inactivation, deletion of γ-34.5 also increases safety and cancer selectivity [22,59,64]. Healthy cells have various anti-viral defense mechanisms.…”

Section: Il-12 Insertion Does Not Compromise Safety and Tumor Specifimentioning

confidence: 99%

Oncolytic Virus Encoding a Master Pro-Inflammatory Cytokine Interleukin 12 in Cancer Immunotherapy

Nguyen

Guz-Montgomery

Saha

2020

Cells

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Oncolytic viruses (OVs) are genetically modified or naturally occurring viruses, which preferentially replicate in and kill cancer cells while sparing healthy cells, and induce anti-tumor immunity. OV-induced tumor immunity can be enhanced through viral expression of anti-tumor cytokines such as interleukin 12 (IL-12). IL-12 is a potent anti-cancer agent that promotes T-helper 1 (Th1) differentiation, facilitates T-cell-mediated killing of cancer cells, and inhibits tumor angiogenesis. Despite success in preclinical models, systemic IL-12 therapy is associated with significant toxicity in humans. Therefore, to utilize the therapeutic potential of IL-12 in OV-based cancer therapy, 25 different IL-12 expressing OVs (OV-IL12s) have been genetically engineered for local IL-12 production and tested preclinically in various cancer models. Among OV-IL12s, oncolytic herpes simplex virus encoding IL-12 (OHSV-IL12) is the furthest along in the clinic. IL-12 expression locally in the tumors avoids systemic toxicity while inducing an efficient anti-tumor immunity and synergizes with anti-angiogenic drugs or immunomodulators without compromising safety. Despite the rapidly rising interest, there are no current reviews on OV-IL12s that exploit their potential efficacy and safety to translate into human subjects. In this article, we will discuss safety, tumor-specificity, and anti-tumor immune/anti-angiogenic effects of OHSV-IL12 as mono-and combination-therapies. In addition to OHSV-IL12 viruses, we will also review other IL-12-expressing OVs and their application in cancer therapy.

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Section: Il-12 Insertion Does Not Compromise Safety and Tumor Specifimentioning

confidence: 99%

Oncolytic Virus Encoding a Master Pro-Inflammatory Cytokine Interleukin 12 in Cancer Immunotherapy

Nguyen

Guz-Montgomery

Saha

2020

Cells

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“…Oncolytic viruses are a distinct class of anti-cancer agents with unique mechanisms of action: selectively replicating in and killing cancer cells (oncolysis), including GBM, spreading in the tumor while sparing normal tissue, and inducing anti-tumor immune responses (Saha et al, 2015). Replication-competent oncolytic herpes simplex viruses (oHSVs) are engineered for oncolytic activity and safety (Peters and Rabkin, 2015).…”

Section: Introductionmentioning

confidence: 99%

Macrophage Polarization Contributes to Glioblastoma Eradication by Combination Immunovirotherapy and Immune Checkpoint Blockade

2017

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Summary Glioblastoma is an immunosuppressive, fatal brain cancer that contains glioblastoma stem-like cells (GSCs). Oncolytic herpes simplex virus (oHSV) selectively replicates in cancer cells, while inducing anti-tumor immunity. OHSV G47Δ expressing murine IL-12 (G47Δ-mIL12), antibodies to immune checkpoints (CTLA-4, PD-1, PD-L1), or dual combinations modestly extended survival of a mouse glioma model. However, the triple combination of anti-CTLA-4, anti-PD-1, and G47Δ-mIL12 cured most mice in two glioma models. This treatment was associated with macrophage influx and M1-like polarization, along with increased T effector to T regulatory cell ratios. Immune cell depletion studies demonstrated that CD4+ and CD8+ T cells as well as macrophages are required for synergistic curative activity. This combination should be translatable to the clinic and other immunosuppressive cancers.

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“…81,82 NCT00390299 is a phase I trial for patients with recurrent GBM, assessing the safety and efficacy of measles virus transfected with human carcinoembryonic antigen as a marker for replication in vivo. 66 The PVSRIPO trial (NCT01491893) is evaluating a recombinant poliovirus (PSVRIPO) and has shown promising early results.…”

Section: Immunotherapy For Gliomamentioning

confidence: 99%

Beyond Alkylating Agents for Gliomas: Quo Vadimus?

Puduvalli

Chaudhary

McClugage

et al. 2017

American Society of Clinical Oncology Educational Book

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OVERVIEW Recent advances in therapies have yielded notable success in terms of improved survival in several cancers. However, such treatments have failed to improve outcome in patients with gliomas for whom surgery followed by radiation therapy and chemotherapy with alkylating agents remain the standard of care. Genetic and epigenetic studies have helped identify several alterations specific to gliomas. Attempts to target these altered pathways have been unsuccessful due to various factors, including tumor heterogeneity, adaptive resistance of tumor cells, and limitations of access across the blood-brain barrier. Novel therapies that circumvent such limitations have been the focus of intense study and include approaches such as immunotherapy, targeting of signaling hubs and metabolic pathways, and use of biologic agents. Immunotherapeutic approaches including tumor-targeted vaccines, immune checkpoint blockade, antibody-drug conjugates, and chimeric antigen receptor–expressing cell therapies are in various stages of clinical trials. Similarly, identification of key metabolic pathways or converging hubs of signaling pathways that are tumor specific have yielded novel targets for therapy of gliomas. In addition, the failure of conventional therapies against gliomas has led to a growing interest among patients in the use of alternative therapies, which in turn has necessitated developing evidence-based approaches to the application of such therapies in clinical studies. The development of these novel approaches bears potential for providing breakthroughs in treatment of more meaningful and improved outcomes for patients with gliomas.

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Exploring the antitumor effect of virus in malignant glioma

Cited by 25 publications

References 139 publications

Oncolytic Virus Encoding a Master Pro-Inflammatory Cytokine Interleukin 12 in Cancer Immunotherapy

Oncolytic Virus Encoding a Master Pro-Inflammatory Cytokine Interleukin 12 in Cancer Immunotherapy

Macrophage Polarization Contributes to Glioblastoma Eradication by Combination Immunovirotherapy and Immune Checkpoint Blockade

Beyond Alkylating Agents for Gliomas: Quo Vadimus?

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