miR-375- and miR-1-Regulated Coxsackievirus B3 Has No Pancreas and Heart Toxicity But Strong Antitumor Efficiency in Colorectal Carcinomas

Hazini, Ahmet; Dieringer, Babette; Pryshliak, Markian; Knoch, Klaus-Peter; Heimann, Lisanne; Tolksdorf, Beatrice; Pappritz, Kathleen; El-Shafeey, Muhammad; Solimena, Michele; Beling, Antje; Kurreck, Jens; Klingel, Karin; Fechner, Henry

doi:10.1089/hum.2020.228

Cited by 17 publications

(36 citation statements)

References 49 publications

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“…Single nucleotide substitutions or small stretches of up to three nucleotide substitutions were detected in some of the copies of the miR-TS. However, at least one copy remained completely intact, which was obviously sufficient to prevent undesirable virus replication and organ-toxicity [107]. In another study Liu et al [105] observed complete loss of miR-TS from an oncolytic CVB3 in some animals 35 days after virus injection resulting in severe side effects in the affected animals.…”

Section: Improvement Of the Safety Of Oncolytic Cvb3 By Microrna-mediated Regulation Of Virus Replicationmentioning

confidence: 99%

“…The CV-B3/2035A strain has oncolytic potential in endometrial carcinoma [91]. The strain H3 is a cardiotropic strain of CVB3 Nancy, which has oncolytic activity in colorectal cancer but induces severe pancreatitis and myocarditis [74,100,107]. CV-B3/2035A is another CVB3 strain which was recently evaluated for its oncolytic activity (Figure 5, Table 1).…”

Section: Cvb3 Strains Their Oncolytic Activity and Treatment-related Side Effectsmentioning

confidence: 99%

“…H3 is a cardiac-adapted laboratory strain of Nancy [100] and 31-1-93 is a derivative of PD obtained after four passages in the mouse heart [102]. Although they possess potent oncolytic activity, each kills nude mice a few days after intratumoral virus injection [92,107] and induces severe pancreatitis and myocarditis in immunocompetent mice [74,77].…”

Section: Cvb3 Strains Their Oncolytic Activity and Treatment-related Side Effectsmentioning

confidence: 99%

“…Nevertheless, several studies recently demonstrated that miR-TS can also be inserted into the 3 -UTR of CVB3 without affecting virus propagation. This was achieved by placing the miR-TS immediately downstream of the stop codon of the CVB3 polyprotein [74,103,[107][108][109]. This approach apparently prevents the destruction of critical secondary structures within the 3 -UTR of the virus.…”

Section: Improvement Of the Safety Of Oncolytic Cvb3 By Microrna-mediated Regulation Of Virus Replicationmentioning

confidence: 99%

“…This involved the insertion of miR-TS in a forward orientation to target the plus-strand genome or in a reverse orientation to target the minus-strand replication intermediate of CVB3. All CVB3 containing miR-TS in their plus-strand genome were sensitive to the corresponding miRs [74,103,105,[107][108][109]137]. The miR-targeting of the viral minus-strand is particularly attractive, as CVB3 generates only few minus-strand RNA intermediates during genome replication, which function as template for generating lots of plus-strand RNA genomes [141].…”

Section: Improvement Of the Safety Of Oncolytic Cvb3 By Microrna-mediated Regulation Of Virus Replicationmentioning

confidence: 99%

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Coxsackievirus B3—Its Potential as an Oncolytic Virus

Geisler

Hazini

Heimann

et al. 2021

Viruses

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Oncolytic virotherapy represents one of the most advanced strategies to treat otherwise untreatable types of cancer. Despite encouraging developments in recent years, the limited fraction of patients responding to therapy has demonstrated the need to search for new suitable viruses. Coxsackievirus B3 (CVB3) is a promising novel candidate with particularly valuable features. Its entry receptor, the coxsackievirus and adenovirus receptor (CAR), and heparan sulfate, which is used for cellular entry by some CVB3 variants, are highly expressed on various cancer types. Consequently, CVB3 has broad anti-tumor activity, as shown in various xenograft and syngeneic mouse tumor models. In addition to direct tumor cell killing the virus induces a strong immune response against the tumor, which contributes to a substantial increase in the efficiency of the treatment. The toxicity of oncolytic CVB3 in healthy tissues is variable and depends on the virus strain. It can be abrogated by genetic engineering the virus with target sites of microRNAs. In this review, we present an overview of the current status of the development of CVB3 as an oncolytic virus and outline which steps still need to be accomplished to develop CVB3 as a therapeutic agent for clinical use in cancer treatment.

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Section: Improvement Of the Safety Of Oncolytic Cvb3 By Microrna-mediated Regulation Of Virus Replicationmentioning

confidence: 99%

Section: Cvb3 Strains Their Oncolytic Activity and Treatment-related Side Effectsmentioning

confidence: 99%

Section: Cvb3 Strains Their Oncolytic Activity and Treatment-related Side Effectsmentioning

confidence: 99%

Section: Improvement Of the Safety Of Oncolytic Cvb3 By Microrna-mediated Regulation Of Virus Replicationmentioning

confidence: 99%

Section: Improvement Of the Safety Of Oncolytic Cvb3 By Microrna-mediated Regulation Of Virus Replicationmentioning

confidence: 99%

See 3 more Smart Citations

Coxsackievirus B3—Its Potential as an Oncolytic Virus

Geisler

Hazini

Heimann

et al. 2021

Viruses

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An intranasal attenuated Coxsackievirus B3 vaccine induces strong systemic and mucosal immunity against CVB3 lethal challenge

Deng,

Li,

et al. 2024

Journal of Medical Virology

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Coxsackievirus B3 (CVB3) triggers viral myocarditis, with no effective vaccine yet. This fecal‐oral transmitted pathogen has prompted interest in mucosal immunization strategies to impede CVB3 spread. We developed a new attenuated vaccine strain, named CVB3(mu). The potential of CVB3(mu) to stimulate mucosal immune protection remains to be elucidated. This study evaluates the attenuation characteristics of CVB3(mu) via a rapid evolution cellular model and RNA sequencing. Its temperature sensitivity and safety were evaluated through in vitro and in vivo experiments. The mucosal immunity protection of CVB3(mu) was assessed via intranasal immunization in Balb/c mice. The results indicate that CVB3(mu) exhibits temperature sensitivity and forms smaller plaques. It sustains fewer genetic mutations and still possesses certain attenuated traits up to the 25th passage, in comparison to CVB3(WT). Intranasal immunization elicited a significant serum neutralizing antibodies, and a substantial sIgA response in nasal washes. In vivo trials revealed CVB3(mu) protection in adult mice and passive protection in suckling mice against lethal CVB3(WT) challenges. In conclusion, CVB3(mu), a live attenuated intranasal vaccine, provides protection involving humoral and mucosal immunity, making it a promising candidate to control CVB3 spread and infection.

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