Combining Vascular Normalization with an Oncolytic Virus Enhances Immunotherapy in a Preclinical Model of Advanced-Stage Ovarian Cancer

Matuszewska, Kathy; Santry, Lisa A.; Vloten, Jacob P. van; AuYeung, Amanda W.K.; Major, Pierre; Lawler, Jack; Wootton, Sarah K.; Bridle, Byram W.; Petrik, Jim

doi:10.1158/1078-0432.ccr-18-0220

Cited by 58 publications

(49 citation statements)

References 78 publications

(97 reference statements)

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“…Mucin 16, α-folate receptor, and mesothelin are being investigated as specific targets of genetic modification of chimeric antigen receptor T (CAR-T) cell therapies for ovarian cancer ( 49 ). Oncolytic viral therapy that utilizes genetic engineering is also being used to create viruses that selectively infect tumor cells and lead to tumor cell lysis ( 11 ). In this section, we have discussed the evolution of immunotherapies for ovarian cancer.…”

Section: Current State Of Ovarian Cancer Immunotherapymentioning

confidence: 99%

Immunotherapy for Ovarian Cancer: Adjuvant, Combination, and Neoadjuvant

et al. 2020

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Ovarian cancer is the most lethal gynecologic malignancy. Surgery and chemotherapy are the primary treatments for ovarian cancer; however, patients often succumb to recurrence with chemotherapeutic resistance within several years after the initial treatment. In the past two decades, immunotherapy has rapidly developed, and has revolutionized the treatment of various types of cancer. Despite the fact that immunotherapy response rates among ovarian cancer patients remain modest, treatment with immune checkpoint inhibitors (ICIs), chimeric antigen receptor (CAR)- and TCR-engineered T cells is rapidly developing. Therapeutic efficiency could be improved significantly if immunotherapy is included as an adjuvant therapy, in combination with chemotherapy, radiation therapy, and the use of anti-angiogenesis drugs, and poly ADP ribose polymerase inhibitors (PARPi). Newly developed technologies that identify therapeutic targets, predict treatment efficacy, rapidly screen potential immunotherapy drugs, provide neoadjuvant immunotherapy, and utilize nanomedicine technology provide new opportunities for the treatment of ovarian cancer, and have the potential to prolong patient survival. However, important issues that may hinder the efficacy of such approaches, including hyperprogressive disease (HPD), immunotherapy-resistance, and toxicity of the treatments, including neurotoxicity, must be taken into account and addressed for these therapies to be effective.

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Section: Current State Of Ovarian Cancer Immunotherapymentioning

confidence: 99%

Immunotherapy for Ovarian Cancer: Adjuvant, Combination, and Neoadjuvant

et al. 2020

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“…In this issue of Clinical Cancer Research, Matuszewska and colleagues report on a novel therapeutic approach incorporating oncolytic therapy with Newcastle Disease Virus (NDV) and vascular targeting in a preclinical model of ovarian cancer (1). Despite the development of a number of novel anticancer agents over the past 20 years, ovarian cancer remains the most lethal gynecologic malignancy.…”

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confidence: 99%

“…These findings present a therapeutic conundrum. Although the disruption of tumor vasculature is commonly seen as one of the mechanisms by which oncolytic viruses destroy tumors (3), vascular shutdown can in fact lead to impaired delivery of oncolytic virus and immune cells to the tumor site (1).…”

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confidence: 99%

“…Remarkably, this led to significant improvement of tumor control, evidenced by a reduction in primary tumor growth, ascites and metastases, when compared with either treatment alone. The authors demonstrate that tumors isolated from the animals treated with combination therapy exhibited increased recruitment and activation of T cells, natural killer (NK) cells, and macrophages, and a reduced production of immunosuppressive cytokines such as TGFb and IL10 (1).…”

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confidence: 99%

“…Finally, as shown in this study, vascular shutdown caused by oncolytic viruses can reduce the ability of the virus to penetrate the tumor and potentially limits T-cell entry. Administration of NDV in combination with 3TSR can counteract this effect, allowing for better trafficking of both the oncolytic virus and immune cells to the tumor site (1).…”

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Virus, Vessel, Victory: A Novel Approach to Tumor Killing

Bykov

Zamarin

2019

Clinical Cancer Research

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Ovarian carcinoma immune‐related microRNA affects the heterogeneity of the endocrine microenvironment and anti‐tumor immune pattern

Gao,

Wang,

Xiang

et al. 2023

The Journal of Gene Medicine

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BackgroundThe eighth‐leading cause of cancer‐related mortality and the seventh‐most prevalent malignancy in women globally is ovarian cancer (OV). However, 5‐year survival expectancy after conventional treatment is not good. Therefore, there is an urgent need for novel signatures to guide the designation of therapeutic schemes for OV patients.MethodsWe used univariate Cox analysis to screen hormone secretion regulation axis‐related microRNAs (miRNAs), least absolute shrinkage and selection operator analysis to select candidate miRNAs and multivariate Cox analysis to build the risk model. To evaluate possible route and functional differences, enrichment analysis using Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) were performed on the differentially expressed genes (DEGs) across various risk groups. We compared Tumor Immune Dysfunction and Exclusion (TIDE) scores across risk categories by analyzing immune cell infiltration, immune checkpoint gene expression, immunological function and TIDE scores. In the end, we determined the half maximal inhibitory concentration (IC50) of chemotherapy and targeted medicines for individual patients. Cell assays were determined to test the migration of the miRNA‐target genes and western blotting was used to test the correlation of the miRNA‐target genes and the pathways.ResultsWe finally identified hormone secretion regulation axis‐related 13 microRNAs to build a risk model. The validation of observed and anticipated values revealed a fair level of agreement. To evaluate the molecular pathways between various groups in accordance with the GO and KEGG analyses, we then discovered 173 DEGs between distinct risk groups. The risk score was shown to be inversely related to the number of immune cells, including myeloid dendritic, granulocytes, M1 and M2 macrophages, B cells, t‐lymphocytes, and CD4+ and CD8+ cells, suggesting that immune cells are more frequent in the low‐risk group. Immune cell infiltration investigation yielded these results. Finally, we recognized 11 chemotherapeutic drugs and 30 novels targeted drugs on the basis of IC50 between the different risk groups. GJB5 was determined to be the mir‐219 target gene and was identified as promoting the cell cycle process. In addition, hormone secretion regulation axis related miRNAs were reported to affects the heterogeneity of endocrine microenvironment and anti‐tumor immune pattern.ConclusionsIn conclusion, a 13‐miRNA prognostic model was constructed to know the immune status, prognosis, immunotherapeutic response and anti‐tumor drug sensitivity for OV, which provides theoretical guidance for the effective and individualized treatment of OV patients.

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Combining Vascular Normalization with an Oncolytic Virus Enhances Immunotherapy in a Preclinical Model of Advanced-Stage Ovarian Cancer

Cited by 58 publications

References 78 publications

Immunotherapy for Ovarian Cancer: Adjuvant, Combination, and Neoadjuvant

Immunotherapy for Ovarian Cancer: Adjuvant, Combination, and Neoadjuvant

Virus, Vessel, Victory: A Novel Approach to Tumor Killing

Ovarian carcinoma immune‐related microRNA affects the heterogeneity of the endocrine microenvironment and anti‐tumor immune pattern

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