A novel fiber chimeric conditionally replicative adenovirus-Ad5/F35 for tumor therapy

Yang, Ming; Yang, Chenghao; Guo, Wenwen; Tang, Jinlong; Huang, Qian; Feng, Shouxin; Jiang, An; Xu, Xianglai; Guan, Jun; Liu, Yan Qun

doi:10.1080/15384047.2017.1395115

Cited by 17 publications

(10 citation statements)

References 95 publications

(99 reference statements)

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“…Swapping of fibers is also an option to change the affinity and evade immune response, at least temporarily [109][110][111][112][113][114]. The swapping of fibers and chimeric fibers has been very promising in early experiments and clinical trials, especially Ad5/3, Ad5/11, Ad5/9, and Ad5/35 [95,[115][116][117][118][119], Since these fibers (Ad3 and Ad35 fibers) do not bind to CAR, detargeting from CAR becomes an inherent property.…”

Section: Detargeting Of Fibermentioning

confidence: 99%

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Oncolytic Adenoviruses: Strategies for Improved Targeting and Specificity

Hajeri

Sharma

Yamamoto

2020

Cancers

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Cancer is a major health problem. Most of the treatments exhibit systemic toxicity, as they are not targeted or specific to cancerous cells and tumors. Adenoviruses are very promising gene delivery vectors and have immense potential to deliver targeted therapy. Here, we review a wide range of strategies that have been tried, tested, and demonstrated to enhance the specificity of oncolytic viruses towards specific cancer cells. A combination of these strategies and other conventional therapies may be more effective than any of those strategies alone.

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Section: Detargeting Of Fibermentioning

confidence: 99%

“…However, this may drive their affinity towards desmoglein, CD46, and other native receptors, leading to a different type of off-target effects. This can be overcome by combining this (swapping) with other strategies, such as adding a targeting peptide, to achieve effective detargeting and retargeting [64,68,112].…”

Section: Detargeting Of Fibermentioning

confidence: 99%

Oncolytic Adenoviruses: Strategies for Improved Targeting and Specificity

Hajeri

Sharma

Yamamoto

2020

Cancers

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“…Currently, oncolytic adenoviruses developed based on fiber-modified Ad5 vectors afford improved effects in cancer therapies in clinical trials, as represented by Ad-RGD 36 , 37 , Ad5/3 10 - 12 , and Ad5/35 14 . Although recombinant Ad5 vectors with full-length Ad37-fiber 38 or Ad37-knob exchange 34 have been generated for purposes of studying the infection mechanisms, to our knowledge no oncolytic adenovirus-based Ad37-fiber/knob chimeric Ad5 has previously been developed.…”

Section: Discussionmentioning

confidence: 99%

“…In addition, considering that tropism of infection 9 often differed between adenovirus subgroups, another main approach to modify or broaden the tropism of Ad5-based vectors is fiber knob serotype switching. Numerous Ad5-based oncolytic vectors with chimeric fibers have been developed, with the most advanced with regard to development as preclinical and clinical cancer therapies being Ad5/3 10 - 12 and Ad5/35 13 , 14 resulting from exchange of the Ad3- and Ad35-fiber/knob, respectively.…”

Section: Introductionmentioning

confidence: 99%

A tropism-transformed Oncolytic Adenovirus with Dual Capsid Modifications for enhanced Glioblastoma Therapy

Wang¹,

Liu²,

Li³

et al. 2020

J. Cancer

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Glioblastoma, the most common human brain tumor, is highly invasive and difficult to cure using conventional cancer therapies. As an alternative, adenovirus-mediated virotherapies represent a popular and maturing technology. However, the cell surface coxsackievirus and adenovirus receptor (CAR)-dependent infection mechanism limits the infectivity and oncolytic effects of Adenovirus type 5. To address this limitation, in this study we aimed to develop a novel oncolytic adenovirus for enhanced infectivity and therapeutic efficacy toward glioblastoma. We developed a novel genetically modified oncolytic adenovirus vector with dual capsid modifications to facilitate infection and specific cytotoxicity toward glioma cells. Modification of the adenoviral capsid proteins involved the incorporation of a synthetic leucine zipper-like dimerization domain into the capsid protein IX (pIX) of human adenovirus serotype 5 (Ad5) and the exchange of the fiber knob from Ad37. The virus infection mechanism and anti-tumor efficacy of modified vectors were evaluated in both in vitro (cell) and in vivo (mouse) models. Ad37-knob exchange efficiently promoted the virus infection and replication-induced glioma cell lysis by oncolytic Ad5. We also found that gene therapy mediated by the dual-modified oncolytic Ad5 vector coupled with the tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) exhibited significantly enhanced anti-tumor efficacy in vitro and in vivo. This genetically modified oncolytic adenovirus provides a promising vector for future use in glioblastoma gene-viral-based therapies.

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“…3 Although the fiber knob domains from different human and nonhuman adenoviruses were tested for their ability to increase the transduction efficacy in tumor cells, 31 the most advanced preclinical/clinical fiber chimeric rAds are Ad5/3-and Ad5/35-based. 32 Ad3 utilizes desmoglein 2 (DSG2) as a primary high-affinity receptor 33 and CD46 as a low-affinity receptor (avidity-binding), 34 while Ad35 uses CD46 as a primary high-affinity receptor. 35 DSG2 and CD46 expression is preserved in tumor cells, 36 including glioma tissues.…”

Section: Introductionmentioning

confidence: 99%

Superior infectivity of the fiber chimeric oncolytic adenoviruses Ad5/35 and Ad5/3 over Ad5-delta-24-RGD in primary glioma cultures

Stepanenko

Сосновцева

Valikhov

et al. 2022

Molecular Therapy - Oncolytics

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Ad5-delta-24-RGD is currently the most clinically advanced recombinant adenovirus (rAd) for glioma therapy. We constructed a panel of fiber-modified rAds (Ad5RGD, Ad5/3, Ad5/35, Ad5/3RGD, and Ad5/35RGD, all harboring the delta-24 modification) and compared their infectivity, replication, reproduction, and cytolytic efficacy in human and rodent glioma cell lines and short-term cultures from primary gliomas. In human cells, both Ad5/35-delta-24 and Ad5/3-delta-24 displayed superior infectivity and cytolytic efficacy over Ad5-delta-24-RGD, while Ad5/3-delta-24-RGD and Ad5/35delta-24-RGD did not show further improvements in efficacy. The expression of the adenoviral receptors/coreceptors CAR, DSG2, and CD46 and the integrins aVb3/aVb5 did not predict the relative cytolytic efficacy of the fiber-modified rAds. The cytotoxicity of the fiber-modified rAds in human primary normal cultures of different origins and in primary glioma cultures was comparable, indicating that the delta-24 modification did not confer tumor cell selectivity. We also revealed that CT-2A and GL261 glioma cells might be used as murine cell models for the fiber chimeric rAds in vitro and in vivo. In GL261 tumor-bearing mice, Ad5/35-delta-24, armed with the immune costimulator OX40L as the E2A/DBP-p2A-mOX40L fusion, produced long-term survivors, which were able to reject tumor cells upon rechallenge. Our data underscore the potential of local Ad5/35-delta-24-based immunovirotherapy for glioblastoma treatment.

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A novel fiber chimeric conditionally replicative adenovirus-Ad5/F35 for tumor therapy

Cited by 17 publications

References 95 publications

Oncolytic Adenoviruses: Strategies for Improved Targeting and Specificity

Oncolytic Adenoviruses: Strategies for Improved Targeting and Specificity

A tropism-transformed Oncolytic Adenovirus with Dual Capsid Modifications for enhanced Glioblastoma Therapy

Superior infectivity of the fiber chimeric oncolytic adenoviruses Ad5/35 and Ad5/3 over Ad5-delta-24-RGD in primary glioma cultures

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