Oncolytic viruses: focusing on the tumor microenvironment

Vries, Christiaan R. de; Kaufman, Howard L.; Lattime, Edmund C.

doi:10.1038/cgt.2015.11

Cited by 16 publications

(16 citation statements)

References 22 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Our findings are corroborated by several studies that have shown that SMCs and innate immune stimuli reduce tumour volume and prolong survival in murine tumour models [8, 16, 21, 26, 27]. Based on the discrepancy in our in vitro and in vivo data, we hypothesize that the effectiveness of this combination therapy relies on bystander killing via cytokines that are released from non-cancer cells in the tumour microenvironment [28]. It has been reported that oncolytic virus infections induce the secretion of cytokines and chemokines that kill cancer cells directly and promote bystander killing through the recruitment and activation of innate and adaptive immune cells that target the tumour [16, 29, 30].…”

Section: Discussionsupporting

confidence: 88%

Oncolytic virus synergizes with Smac mimetic compounds to induce rhabdomyosarcoma cell death in a syngeneic murine model

et al. 2016

View full text Add to dashboard Cite

Rhabdomyosarcoma (RMS), a neoplasm characterized by undifferentiated myoblasts, is the most common soft tissue tumour in children. Therapeutic resistance is common in RMS and is often caused by acquired defects in the cellular apoptotic program. Smac mimetic compounds (SMCs) are a novel class of inhibitor of apoptosis (IAP) antagonists that are currently under clinical development as cancer therapeutics. We previously reported that cIAP1 is overexpressed in human primary RMS tumours and in patient-derived RMS cell lines where it drives resistance to apoptosis. In this study, we investigated whether inflammatory cytokine production triggered by activators of innate immunity synergizes with LCL161 to induce bystander killing of RMS cells in vitro and in vivo. Indeed, we show that innate immune stimuli (oncolytic virus (VSVΔ51-GFP), interferon γ (IFNγ), and tumour necrosis factor-like weak inducer of apoptosis (TWEAK)) combine with SMCs in vitro to reduce cell viability in the Kym-1 RMS cancer cell line. Other human RMS cell lines (RH36, RH41, RD, RH18, RH28, and RH30) and the murine RMS cell line 76-9 are resistant to treatment with LCL161 alone or in combination with immune stimulants in in vitro cell viability assays. In contrast, we report that the combination of LCL161 and VSVΔ51-GFP reduces tumour volume and prolongs survival in a 76-9 syngeneic murine model. Our results support further exploration of the combined use of IAP antagonists and innate immune stimuli as a therapeutic approach for RMS cancers.

show abstract

Section: Discussionsupporting

confidence: 88%

Oncolytic virus synergizes with Smac mimetic compounds to induce rhabdomyosarcoma cell death in a syngeneic murine model

et al. 2016

View full text Add to dashboard Cite

show abstract

“…Oncolytic viruses have had an impact on melanoma presumably through their effects not only directly on tumor cells but also by activating innate immunity and inducing tumor-specific immunity thus effectively reducing immune suppression in the TME [232]. Alternatively, intratumoral approaches that mimic viral infection such as intratumoral injections of poly-ICLC [233] or CpG [234], but without its associated side effects of inducing dominant antiviral immunity would be preferable [235]. Another possible method to modulate the TME is through direct activation of the STING pathway.…”

Section: In Combinationmentioning

confidence: 99%

Dendritic cell-based immunotherapy

2016

View full text Add to dashboard Cite

Immunotherapy using dendritic cell (DC)-based vaccination is an approved approach for harnessing the potential of a patient's own immune system to eliminate tumor cells in metastatic hormone-refractory cancer. Overall, although many DC vaccines have been tested in the clinic and proven to be immunogenic, and in some cases associated with clinical outcome, there remains no consensus on how to manufacture DC vaccines. In this review we will discuss what has been learned thus far about human DC biology from clinical studies, and how current approaches to apply DC vaccines in the clinic could be improved to enhance anti-tumor immunity.

show abstract

“…In a recent editorial, de Vries et al emphasized that the most successful OV-based strategy will be the one taking advantage of these viruses’ capacity for modifying the tumor microenvironment [ 52 ]. Indeed, several OVs were reported to exert positive effects in regard to tumor microenvironment modulation.…”

Section: Other Oncolytic Viruses and Tumor Microenvironment Modulamentioning

confidence: 99%

Immunotherapeutic Potential of Oncolytic H-1 Parvovirus: Hints of Glioblastoma Microenvironment Conversion towards Immunogenicity

Angelova

Barf

Geletneky

et al. 2017

Viruses

View full text Add to dashboard Cite

Glioblastoma, one of the most aggressive primary brain tumors, is characterized by highly immunosuppressive microenvironment. This contributes to glioblastoma resistance to standard treatment modalities and allows tumor growth and recurrence. Several immune-targeted approaches have been recently developed and are currently under preclinical and clinical investigation. Oncolytic viruses, including the autonomous protoparvovirus H-1 (H-1PV), show great promise as novel immunotherapeutic tools. In a first phase I/IIa clinical trial (ParvOryx01), H-1PV was safe and well tolerated when locally or systemically administered to recurrent glioblastoma patients. The virus was able to cross the blood–brain (tumor) barrier after intravenous infusion. Importantly, H-1PV treatment of glioblastoma patients was associated with immunogenic changes in the tumor microenvironment. Tumor infiltration with activated cytotoxic T cells, induction of cathepsin B and inducible nitric oxide (NO) synthase (iNOS) expression in tumor-associated microglia/macrophages (TAM), and accumulation of activated TAM in cluster of differentiation (CD) 40 ligand (CD40L)-positive glioblastoma regions was detected. These are the first-in-human observations of H-1PV capacity to switch the immunosuppressed tumor microenvironment towards immunogenicity. Based on this pilot study, we present a tentative model of H-1PV-mediated modulation of glioblastoma microenvironment and propose a combinatorial therapeutic approach taking advantage of H-1PV-induced microglia/macrophage activation for further (pre)clinical testing.

show abstract

Oncolytic viruses: focusing on the tumor microenvironment

Cited by 16 publications

References 22 publications

Oncolytic virus synergizes with Smac mimetic compounds to induce rhabdomyosarcoma cell death in a syngeneic murine model

Oncolytic virus synergizes with Smac mimetic compounds to induce rhabdomyosarcoma cell death in a syngeneic murine model

Dendritic cell-based immunotherapy

Immunotherapeutic Potential of Oncolytic H-1 Parvovirus: Hints of Glioblastoma Microenvironment Conversion towards Immunogenicity

Contact Info

Product

Resources

About