Oncolytic Urabe mumps virus: A promising virotherapy for triple-negative breast cancer

Behrens, Marshall D.; Stiles, Robert J; Pike, Gennett M.; Sikkink, Laura A.; Zhuang, Yongxian; Yu, Jia; Wang, L.; Boughey, Judy C.; Goetz, Matthew P.; Federspiel, Mark J.

doi:10.1016/j.omto.2022.11.002

Cited by 9 publications

(7 citation statements)

References 21 publications

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“…Mumps virus is an enveloped, negative-sense RNA virus from the genus Orthorubulavirus in the family Paramyxoviridae . Samples of mumps virus used in the clinical trials described earlier in this review were obtained with the goal of continuing its development as an OV [ 158 ]. Since it was known that the original source material was not composed of purified viruses, the sample obtained from Japan was designated as MuV-U-Japan, and the subtypes within were isolated and studied for their oncolytic potential.…”

Section: Preclinical Ovs For Tnbcmentioning

confidence: 99%

Triple-Negative Breast Cancer: Basic Biology and Immuno-Oncolytic Viruses

Monaco

Idris

Essani

2023

Cancers

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Triple-negative breast cancer (TNBC) is the most lethal subtype of breast cancer. TNBC diagnoses account for approximately one-fifth of all breast cancer cases globally. The lack of receptors for estrogen, progesterone, and human epidermal growth factor 2 (HER-2, CD340) results in a lack of available molecular-based therapeutics. This increases the difficulty of treatment and leaves more traditional as well as toxic therapies as the only available standards of care in many cases. Recurrence is an additional serious problem, contributing substantially to its higher mortality rate as compared to other breast cancers. Tumor heterogeneity also poses a large obstacle to treatment approaches. No driver of tumor development has been identified for TNBC, and large variations in mutational burden between tumors have been described previously. Here, we describe the biology of six different subtypes of TNBC, based on differential gene expression. Subtype differences can have a large impact on metastatic potential and resistance to treatment. Emerging antibody-based therapeutics, such as immune checkpoint inhibitors, have available targets for small subsets of TNBC patients, leading to partial responses and relatively low overall efficacy. Immuno-oncolytic viruses (OVs) have recently become significant in the pursuit of effective treatments for TNBC. OVs generally share the ability to ignore the heterogeneous nature of TNBC cells and allow infection throughout a treated tumor. Recent genetic engineering has allowed for the enhancement of efficacy against certain tumor types while avoiding the most common side effects in non-cancerous tissues. In this review, TNBC is described in order to address the challenges it presents to potential treatments. The OVs currently described preclinically and in various stages of clinical trials are also summarized, as are their strategies to enhance therapeutic potential.

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Section: Preclinical Ovs For Tnbcmentioning

confidence: 99%

Triple-Negative Breast Cancer: Basic Biology and Immuno-Oncolytic Viruses

Monaco

Idris

Essani

2023

Cancers

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“…Impressively, patient-derived organoids may also be employed for oncolytic virotherapy testing, thereby potentially endorsing the establishment of this novel type of multi-mechanistic targeted agent for TNBC immunotherapy. With a view to quantifying their susceptibility to oncolytic virotherapies, Behrens et al, employed a sample of the actual original oncolytic Urabe MuV clinical trial virus stock (MuV-U-Japan) and reported that the two isolates, MuV-UA and MuV-UC, exhibited efficient killing activity against TNBC patient-derived xenograft cell lines grown as three-dimensional organoids that were resistant to standard anthracycline- and taxane-based chemotherapy [ 37 ]. In the same context, Huang et al, explored the tumor suppressor and immune-activating effects of an in-situ DC vaccine (HELA-Exos) in immunocompetent mice and TNBC patient-derived organoids and showed that HELA-Exos possessed a profound ability to augment type one conventional dendritic cell (cDC1) antigen cross-presentation and tumor-reactive CD8+ T-cell generation, hence leading to potent TNBC inhibition [ 38 ].…”

Section: The Use Of Tnbc Organoids For Chemotherapy Sensitivity Testingmentioning

confidence: 99%

The Role of Patient-Derived Organoids in Triple-Negative Breast Cancer Drug Screening

et al. 2023

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Triple-negative breast cancer (TNBC) is one of the most aggressive breast cancer subtypes, with a grave prognosis and few effective treatment options. Organoids represent revolutionary three-dimensional cell culture models, derived from stem or differentiated cells and preserving the capacity to differentiate into the cell types of their tissue of origin. The current review aims at studying the potential of patient-derived TNBC organoids for drug sensitivity testing as well as highlighting the advantages of the organoid technology in terms of drug screening. In order to identify relevant studies, a literature review was conducted using the MEDLINE and LIVIVO databases. The search terms “organoid” and “triple-negative breast cancer” were employed, and we were able to identify 25 studies published between 2018 and 2022. The current manuscript represents the first comprehensive review of the literature focusing on the use of patient-derived organoids for drug sensitivity testing in TNBC. Patient-derived organoids are excellent in vitro study models capable of promoting personalized TNBC therapy by reflecting the treatment responses of the corresponding patients and exhibiting high predictive value in the context of patient survival evaluation.

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“…The roles of paramyxovirus proteins, including HN and M (NDV) [17,35,36], N and P (measles virus) [13,37], M (PPRV) [12], and V (mumps virus) [33], in apoptosis or survival of transformed cells have been examined. Although the oncolytic activity of the mumps virus has been previously validated in some studies [18,30,[38][39][40], it has been shown that the mumps virus V protein modulates apoptosis in cervical adenocarcinoma cancer cells [16].…”

Section: Plos Onementioning

confidence: 99%

The power of mumps virus: Matrix protein activates apoptotic pathways in human colorectal cell lines

Morovati,

Mohammadi,

Masoudi

et al. 2023

PLoS ONE

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New therapeutic approaches can significantly impact the control of colorectal cancer (CRC), which is increasing worldwide. In this study, we investigated the potential of targeting viral proteins to combat cancer cells. Specifically, we examined the anticancer potential of the matrix (M) protein of the mumps virus Hoshino strain in SW480 CRC cell lines. To begin, we individually transfected SW480 cells with pcDNA3 plasmids containing the mumps virus M gene. We then investigated the percentage of cell death, caspase activity, and the expression levels of genes involved in apoptosis pathways. Following this, we performed bioinformatics analysis on the M protein to identify any similarities with Bcl-2 family members and their viral homologs. Our diagnostic methods showed that treatment with the mumps M protein induced apoptosis and upregulated the expression and activity of pro-apoptotic proteins in SW480 CRC cells compared to the control and vector groups. Based on our bioinformatics studies, we proposed that the BH3 motif in the M protein may trigger apoptosis in CRC cells by interacting with cellular Bax. Overall, our study showed for the first time that the mumps virus M protein could be considered as a targeted treatment for CRC by inducing apoptotic pathways.

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Oncolytic Urabe mumps virus: A promising virotherapy for triple-negative breast cancer

Cited by 9 publications

References 21 publications

Triple-Negative Breast Cancer: Basic Biology and Immuno-Oncolytic Viruses

Triple-Negative Breast Cancer: Basic Biology and Immuno-Oncolytic Viruses

The Role of Patient-Derived Organoids in Triple-Negative Breast Cancer Drug Screening

The power of mumps virus: Matrix protein activates apoptotic pathways in human colorectal cell lines

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