Photoactivatable oncolytic adenovirus for optogenetic cancer therapy

Hagihara, Yasuko; Sakamoto, Ayaka; Tokuda, Takashi; Yamashita, Tomoki; Ikemoto, Sena; Kimura, Ayaka; Haruta, Makito; Sasagawa, Kiyotaka; Ohta, Jun; Takayama, Kazuo; Mizuguchi, Hiroyuki

doi:10.1038/s41419-020-02782-6

Cited by 14 publications

(7 citation statements)

References 22 publications

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“…Since the recent FDA approval of talimogene laherpaprevec (T-vec) in 2015 ( Andtbacka et al, 2015 ; Johnson et al, 2015 ), oncolytic virus immunotherapy as a new therapeutic method has attracted more and more attention. A series of mammalian viruses and their genetically engineered forms have been classified as oncolytic viruses, including adenovirus ( Hagihara et al, 2020 ), poxvirus ( Chaurasiya et al, 2020 ), HSV-1 ( Nakashima et al, 2018 ), Newcastle disease virus (NDV) ( Burman et al, 2020 ), alphavirus ( Liu et al, 2020 ), reovirus ( Mahalingam et al, 2018 ) and so on. These oncolytic viruses share the common feature of the ability to selectively self-amplify in tumor cells and kill tumor cells without cytotoxicity to normal cells.…”

Section: Discussionmentioning

confidence: 99%

The Combined Use of Orf Virus and PAK4 Inhibitor Exerts Anti-tumor Effect in Breast Cancer

et al. 2022

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The parapoxvirus Orf virus (ORFV) has long been recognized as one of the valuable vectors in researches of oncolytic virus. In order to develop a potential therapeutic strategy for breast cancer based on the oncolytic virotherapy via ORFV, firstly we explore the oncolytic effects of ORFV. Our research showed that ORFV exerts anti-tumor effects in vitro by inducing breast cancer cell G2/M phase arrest and cell apoptosis. In vivo experiments were carried out, in which we treated 4T1 tumor-bearing BALB/C mice via intratumoral injection of ORFV. ORFV can exert anti-tumor activity by regulating tumor microenvironment (TME) and inducing a host immune response plus directly oncolytic effect. The CRISPR-Cas9 knockout library targeting 507 kinases was used to screen out PAK4, which is beneficial to the anti-tumor effect of ORFV on breast cancer cells. PF-3758309 is a potent PAK4-targeted inhibitor. Co-using of ORFV and PF-3758309 as a combination treatment produces its anti-tumor effects through inhibition of cell viability, induction of apoptosis and suppression of cell migration and invasion in vitro. The results of in vivo experiments showed that the tumor growth of mice in the combination treatment group was significantly inhibited, which proved that the combination treatment exerts an effective anti-tumor effect in vivo. In summary, we have clarified the oncolytic effect of ORFV on breast cancer, and found that the combination of ORFV and PAK4 inhibitor can effectively improve the oncolytic effect of ORFV. We hope our research could provide a new idea for the development of new treatment strategies for breast cancer.

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Section: Discussionmentioning

confidence: 99%

The Combined Use of Orf Virus and PAK4 Inhibitor Exerts Anti-tumor Effect in Breast Cancer

et al. 2022

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“…The in vivo growth of HCC cells was measured using a nude mice model ( 38 , 39 ). All animal experiments were approved by the Institutional Animal Care and Use Committee of the Chinese PLA General Hospital, China.…”

Section: Methodsmentioning

confidence: 99%

The Disassociation of the A20/HSP90 Complex via Downregulation of HSP90 Restores the Effect of A20 Enhancing the Sensitivity of Hepatocellular Carcinoma Cells to Molecular Targeted Agents

et al. 2021

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NF-κB (nuclear factor κB) is a regulator of hepatocellular cancer (HCC)-related inflammation and enhances HCC cells’ resistance to antitumor therapies by promoting cell survival and anti-apoptosis processes. In the present work, we demonstrate that A20, a dominant-negative regulator of NF-κB, forms a complex with HSP90 (heat-shock protein 90) and causes the disassociation of the A20/HSP90 complex via downregulation of HSP90. This process restores the antitumor activation of A20. In clinical specimens, the expression level of A20 did not relate with the outcome in patients receiving sorafenib; however, high levels of HSP90 were associated with poor outcomes in these patients. A20 interacted with and formed complexes with HSP90. Knockdown of HSP90 and treatment with an HSP90 inhibitor disassociated the A20/HSP90 complex. Overexpression of A20 alone did not affect HCC cells. Downregulation of HSP90 combined with A20 overexpression restored the effect of A20. Overexpression of A20 repressed the expression of pro-survival and anti-apoptosis-related factors and enhanced HCC cells’ sensitivity to sorafenib. These results suggest that interactions with HSP90 could be potential mechanisms of A20 inactivation and disassociation of the A20/HSP90 complex and could serve as a novel strategy for HCC treatment.

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“…Tumor growth was significantly inhibited by infection with a photoactivatable oncolytic adenovirus (paOAd), followed by blue light irradiation in vitro and in vivo . In addition, paOAd also showed a therapeutic effect on cancer stem cells [ 42 ]. Expression of p14 FAST from adenovirus can induce widespread syncytium formation, reduce the tumor growth rate, and improve vector efficacy for cancer treatment [ 28 ].…”

Section: Dna Virusesmentioning

confidence: 99%

Viruses as tools in gene therapy, vaccine development, and cancer treatment

et al. 2022

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Using viruses to our advantage has been a huge leap for humanity. Their ability to mediate horizontal gene transfer has made them useful tools for gene therapy, vaccine development, and cancer treatment. Adenoviruses, adeno-associated viruses, retroviruses, lentiviruses, alphaviruses, and herpesviruses are a few of the most common candidates for use as therapeutic agents or efficient gene delivery systems. Efforts are being made to improve and perfect viral-vector-based therapies to overcome potential or reported drawbacks. Some preclinical trials of viral vector vaccines have yielded positive results, indicating their potential as prophylactic or therapeutic vaccine candidates. Utilization of the oncolytic activity of viruses is the future of cancer therapy, as patients will then be free from the harmful effects of chemo- or radiotherapy. This review discusses in vitro and in vivo studies showing the brilliant therapeutic potential of viruses.

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Photoactivatable oncolytic adenovirus for optogenetic cancer therapy

Cited by 14 publications

References 22 publications

The Combined Use of Orf Virus and PAK4 Inhibitor Exerts Anti-tumor Effect in Breast Cancer

The Combined Use of Orf Virus and PAK4 Inhibitor Exerts Anti-tumor Effect in Breast Cancer

The Disassociation of the A20/HSP90 Complex via Downregulation of HSP90 Restores the Effect of A20 Enhancing the Sensitivity of Hepatocellular Carcinoma Cells to Molecular Targeted Agents

Viruses as tools in gene therapy, vaccine development, and cancer treatment

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