Therapeutic targeting of liver cancer with a recombinant DNA vaccine containing the hemagglutinin-neuraminidase gene of Newcastle disease virus via apoptotic-dependent pathways

Chen, Ligang; Yuan-sheng, Liu; Zheng, Tang‐Hui; Chen, Xu; Li, Ping; Xiao, Chuanxing; Ren, Jianlin

doi:10.3892/ol.2016.5114

Cited by 2 publications

(2 citation statements)

References 29 publications

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“…In addition to the investigations incorporating apoptotic antigens for developing DNA vaccines [ 43 , 44 ], some studies attempted to increase the efficacy of such vaccines by modulating apoptotic pathways through the administration of pro-apoptotic adjuvants [ 45 , 46 ]. In this regard, the incorporation of mutant pro-apoptotic caspases and influenza hemagglutinin DNA vaccine induced an augmentation in T helper (Th)2-associated immune responses (IL-4 and IgG1) and an enhancement in CD4+ T cell activation, highlighting the high adjuvant capacity of apoptosis-inducing reagents in developing DNA vaccines [ 47 ].…”

Section: Discussionmentioning

confidence: 99%

Enhanced synergistic antitumor effect of a DNA vaccine with anticancer cytokine, MDA-7/IL-24, and immune checkpoint blockade

Miri

Pourhossein

Hosseini

et al. 2022

Virol J

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Background MDA-7/IL-24 cytokine has shown potent antitumor properties in various types of cancer without exerting any significant toxicity on healthy cells. It has also been proved to encompass pro-immune Th1 cytokine-like behavior. Several E7 DNA vaccines have developed against human papillomavirus (HPV)-related cervical cancer. However, the restricted immunogenicity has limited their clinical applications individually. To address this deficiency, we investigated whether combining the E7 DNA vaccine with MDA-7/IL-24 as an adjuvant would elicit efficient antitumor responses in tumor-bearing mouse models. Next, we evaluated how suppression of immunosuppressive IL-10 cytokine would enhance the outcome of our candidate adjuvant vaccine. Methods For this purpose, tumor-bearing mice received either E7 DNA vaccine, MDA-7/IL-24 cytokine or combination of E7 vaccine with MDA-7/IL-24 adjuvant one week after tumor challenge and boosted two times with one-week interval. IL-10 blockade was performed by injection of anti-IL-10 mAb before each immunization. One week after the last immunization, mice were sacrificed and the treatment efficacy was evaluated through immunological and immunohistochemical analysis. Moreover, the condition of tumors was monitored every two days for six weeks intervals from week 2 on, and the tumor volume was measured and compared within different groups. Results A highly significant synergistic relationship was observed between the E7 DNA vaccine and the MDA-7/IL-24 cytokine against HPV-16+ cervical cancer models. An increase in proliferation of lymphocytes, cytotoxicity of CD8+ T cells, the level of Th1 cytokines (IFN-γ, TNF-α) and IL-4, the level of apoptotic markers (TRAIL and caspase-9), and a decrease in the level of immunosuppressive IL-10 cytokine, together with the control of tumor growth and the induction of tumor regression, all prove the efficacy of adjuvant E7&IL-24 vaccine when compared to their individual administration. Surprisingly, vaccination with the DNA E7&IL-24 significantly reduced the population of Regulatory T cells (Treg) in the spleen of immunized mice compared to sole administration and control groups. Moreover, IL-10 blockade enhanced the effect of the co-administration by eliciting higher levels of IFN-γ and caspase-9, reducing Il-10 secretion and provoking the regression of tumor size. Conclusion The synergy between the E7 DNA vaccine and MDA-7/IL-24 suggests that DNA vaccines’ low immunogenicity can be effectively addressed by coupling them with an immunoregulatory agent. Moreover, IL-10 blockade can be considered a complementary treatment to improve the outcome of conventional or novel cancer therapies.

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Section: Discussionmentioning

confidence: 99%

Enhanced synergistic antitumor effect of a DNA vaccine with anticancer cytokine, MDA-7/IL-24, and immune checkpoint blockade

Miri

Pourhossein

Hosseini

et al. 2022

Virol J

View full text Add to dashboard Cite

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“…Therefore, novel treatment strategies are urgently needed to eliminate cancer cells effectively. Chen et al (2016 )demonstrated that a recombinant DNA vaccine containing the NDV HN gene inhibits hepatocellular carcinoma cell proliferation (HCC). Furthermore, it induces autophagy via the mitochondrial pathway in vitro and in vivo .…”

Section: Preclinical Application Of Newcastle Disease Virus In Variou...mentioning

confidence: 99%

Development of Molecular Mechanisms and Their Application on Oncolytic Newcastle Disease Virus in Cancer Therapy

Huang

Dai

Zhang

et al. 2022

Front. Mol. Biosci.

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Cancer is caused by the destruction or mutation of cellular genetic materials induced by environmental or genetic factors. It is defined by uncontrolled cell proliferation and abnormality of the apoptotic pathways. The majority of human malignancies are characterized by distant metastasis and dissemination. Currently, the most common means of cancer treatment include surgery, radiotherapy, and chemotherapy, which usually damage healthy cells and cause toxicity in patients. Targeted therapy is an effective tumor treatment method with few side effects. At present, some targeted therapeutic drugs have achieved encouraging results in clinical studies, but finding an effective solution to improve the targeting and delivery efficiency of these drugs remains a challenge. In recent years, oncolytic viruses (OVs) have been used to direct the tumor-targeted therapy or immunotherapy. Newcastle disease virus (NDV) is a solid oncolytic agent capable of directly killing tumor cells and increasing tumor antigen exposure. Simultaneously, NDV can trigger the proliferation of tumor-specific immune cells and thus improve the therapeutic efficacy of NDV in cancer. Based on NDV’s inherent oncolytic activity and the stimulation of antitumor immune responses, the combination of NDV and other tumor therapy approaches can improve the antitumor efficacy while reducing drug toxicity, indicating a broad application potential. We discussed the biological properties of NDV, the antitumor molecular mechanisms of oncolytic NDV, and its application in the field of tumor therapy in this review. Furthermore, we presented new insights into the challenges that NDV will confront and suggestions for increasing NDV’s therapeutic efficacy in cancer.

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Therapeutic targeting of liver cancer with a recombinant DNA vaccine containing the hemagglutinin-neuraminidase gene of Newcastle disease virus via apoptotic-dependent pathways

Cited by 2 publications

References 29 publications

Enhanced synergistic antitumor effect of a DNA vaccine with anticancer cytokine, MDA-7/IL-24, and immune checkpoint blockade

Enhanced synergistic antitumor effect of a DNA vaccine with anticancer cytokine, MDA-7/IL-24, and immune checkpoint blockade

Development of Molecular Mechanisms and Their Application on Oncolytic Newcastle Disease Virus in Cancer Therapy

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