Antitumor effect and safety profile of systemically delivered oncolytic adenovirus complexed with EGFR-targeted PAMAM-based dendrimer in orthotopic lung tumor model

Yoon, A-Rum; Kasala, Dayananda; Li, Yan; Hong, Jin; Lee, Wonsig; Jung, Soo‐Jung; Yun, Chae Ok

doi:10.1016/j.jconrel.2016.02.046

Cited by 49 publications

(34 citation statements)

References 61 publications

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“…Tissue penetration can be problematic specifically in cancers like pancreatic cancer, where the cancer tissue is often surrounded by a pronounced accumulation of ECM macromolecules (Li et al, ). With the aim of producing cancer cell‐specific virus replication and enhanced antitumor effects, oncolytic adenoviral vectors and decorin have been tested in various combinations with other genes (Yoon et al, ; Oh et al, ; Li et al, ). For example, in an orthotopic breast cancer model, using oncolytic adenoviral decorin‐IL‐12‐vector resulted in enhanced anti‐tumorigenic immune activity in weakly immunogenic BABL/c mice (Oh et al, ).…”

Section: Decorin – Structure Interactions and Functionsmentioning

confidence: 99%

Decorin‐mediated oncosuppression – a potential future adjuvant therapy for human epithelial cancers

Sainio

Järveläinen

2018

British J Pharmacology

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Currently, the multifaceted role of the extracellular matrix (ECM) in tumourigenesis has been realized. One ECM macromolecule exhibiting potent oncosuppressive actions in tumourigenesis is decorin, the prototype of the small leucine‐rich proteoglycan gene family. The actions of decorin include its ability to function as an endogenous pan‐receptor tyrosine kinase inhibitor, a regulator of both autophagy and mitophagy, as well as a modulator of the immune system. In this review, we will discuss these topics in more detail. We also provide a summary of preclinical studies exploring the value of decorin‐mediated oncosuppression, as a potential future adjuvant therapy for epithelial cancers.Linked ArticlesThis article is part of a themed section on Translating the Matrix. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v176.1/issuetoc

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Section: Decorin – Structure Interactions and Functionsmentioning

confidence: 99%

Decorin‐mediated oncosuppression – a potential future adjuvant therapy for human epithelial cancers

Sainio

Järveläinen

2018

British J Pharmacology

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“…After 2 or 5 days of incubation, the cell pellets and supernatants were collected and freeze-thawed 3 times to harvest the virions. qRT-PCR (Q-PCR; TaqMan PCR detection; Applied Biosystems) was used to assess the number of viral genomes in each sample as described previously (27). Data were processed using the SDS 19.1 Software Package (Applied Biosystems).…”

Section: Viral Production Of Hcc-targeting Oad In Mscsmentioning

confidence: 99%

“…To assess the rate of Ad clearance from the blood, qPCR was performed with whole-blood samples from oAd-treated mice as described previously (27). Blood was collected from retro-orbital plexus of mice at 5 minutes, 10 minutes, 30 minutes, 1 hours, 6 hours, 24 hours, and 48 hours postsystemic injection with 5 Â 10 8 VPs of naked HCC-oAd-WNTi or HCC-oAd-WNTi/MSC (n ¼ 3).…”

Section: Pharmacokinetic Profilementioning

confidence: 99%

“…Hep3B tumor-bearing mice were systemically treated twice in similar manner as above. The lung, heart, stomach, spleen, liver, tumor tissues, and blood were harvested from mice in each group at 24 hours after the second injection, then DNA extraction and qPCR were performed as described previously (27).…”

Section: Biodistribution Profilementioning

confidence: 99%

“…Of note, the HCC-oAd-WNTi/MSC was estimated to harbor 8.0 Â 10 6 VP of oAd based on the results from Supplementary Fig. S2, which meant that the injected dose was 2,500-fold lower than the oAd dose ($2 Â 10 10 VPs) frequently utilized for systemic treatment of tumor-bearing mice (27). These results suggest that loading of oAd into MSCs augments the therapeutic efficacy of systemically administered virus while minimizing any potential dose-related side effects.…”

Section: Potent Therapeutic Efficacy Of Systemically Delivered Hcc-oamentioning

confidence: 99%

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Mesenchymal Stem Cell–Mediated Delivery of an Oncolytic Adenovirus Enhances Antitumor Efficacy in Hepatocellular Carcinoma

Yoon

Hong

et al. 2019

Cancer Research

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Oncolytic virotherapy is a promising alternative to conventional treatment, yet systemic delivery of these viruses to tumors remains a major challenge. In this regard, mesenchymal stem cells (MSC) with well-established tumor-homing property could serve as a promising systemic delivery tool. We showed that MSCs could be effectively infected by hepatocellular carcinoma (HCC)-targeted oncolytic adenovirus (HCC-oAd) through modification of the virus' fiber domain and that the virus replicated efficiently in the cell carrier. HCCtargeting oAd loaded in MSCs (HCC-oAd/MSC) effectively lysed HCC cells in vitro under both normoxic and hypoxic conditions as a result of the hypoxia responsiveness of HCC-oAd. Importantly, systemically administered HCC-oAd/MSC, which were initially infected with a low viral dose, homed to HCC tumors and resulted in a high level of virion accumulation in the tumors, ultimately leading to potent tumor growth inhibition. Furthermore, viral dose reduction and tumor localization of HCC-oAd/MSC prevented the induction of hepatotoxicity by attenuating HCC-oAd hepatic accumulation. Taken together, these results demonstrate that MSCmediated systemic delivery of oAd is a promising strategy for achieving synergistic antitumor efficacy with improved safety profiles. Significance: Mesenchymal stem cells enable delivery of an oncolytic adenovirus specifically to the tumor without posing any risk associated with systemic administration of naked virions to the host.

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Retargeting adenoviruses for therapeutic applications and vaccines

Barry

Rubin

2020

FEBS Letters

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Adenoviruses (Ads) are robust vectors for therapeutic applications and vaccines, but their use can be limited by differences in their in vitro and in vivo pharmacologies. This review emphasizes that there is not just one Ad, but a whole virome of diverse viruses that can be used as therapeutics. It discusses that true vector targeting involves not only retargeting viruses, but importantly also detargeting the viruses from off-target cells.

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Antitumor effect and safety profile of systemically delivered oncolytic adenovirus complexed with EGFR-targeted PAMAM-based dendrimer in orthotopic lung tumor model

Cited by 49 publications

References 61 publications

Decorin‐mediated oncosuppression – a potential future adjuvant therapy for human epithelial cancers

Decorin‐mediated oncosuppression – a potential future adjuvant therapy for human epithelial cancers

Mesenchymal Stem Cell–Mediated Delivery of an Oncolytic Adenovirus Enhances Antitumor Efficacy in Hepatocellular Carcinoma

Retargeting adenoviruses for therapeutic applications and vaccines

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