Adenoviruses for treatment of cancer

Anna Kanerva, Akseli Hemminki

    Research output: Contribution to journalArticleScientificpeer-review

    Abstract

    Most cases of cancer, when detected at an advanced stage, cannot be cured with conventional therapeutic modalities. Therefore, novel targeted approaches such as gene therapy are needed. Nevertheless, while the safety record of gene therapy for cancer has been excellent with more than a thousand patients treated without mortality related to the therapy, clinical efficacy has so far been limited. Moreover, it has become evident that clinical efficacy is partly determined by efficacy of gene delivery. Most adenoviruses used for gene therapy have been based on serotype 5 (Ad5). Unfortunately, recent data suggest that the primary receptor, the coxsackie-adenovirus receptor (CAR) expression in tumors may be highly variable resulting in resistance to adenovirus infection. Consequently, various strategies have been evaluated to modify adenovirus tropism in order to circumvent CAR deficiency, including retargeting complexes or genetic capsid modifications. To further improve tumor penetration and local amplification of the anti-tumor effect, selectively oncolytic agents, e.g. conditionally replicating adenoviruses (CRAds), have been constructed. Infection of tumor cells results in replication, oncolysis, and subsequent release of the virus progeny. Normal tissue is spared due to lack of replication. This review will focus on a discussion of various modifications of adenovirus to achieve efficient anti-tumor effect, and special emphasis will be placed on CRAds in multimodality treatments.
    Original languageEnglish
    JournalAnnals of Medicine
    Volume37
    Pages (from-to)33-43
    Number of pages11
    ISSN0785-3890
    DOIs
    Publication statusPublished - 2005
    MoE publication typeA1 Journal article-refereed

    Cite this

    Kanerva, Anna ; Hemminki, Akseli. / Adenoviruses for treatment of cancer. In: Annals of Medicine. 2005 ; Vol. 37. pp. 33-43.
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    title = "Adenoviruses for treatment of cancer",
    abstract = "Most cases of cancer, when detected at an advanced stage, cannot be cured with conventional therapeutic modalities. Therefore, novel targeted approaches such as gene therapy are needed. Nevertheless, while the safety record of gene therapy for cancer has been excellent with more than a thousand patients treated without mortality related to the therapy, clinical efficacy has so far been limited. Moreover, it has become evident that clinical efficacy is partly determined by efficacy of gene delivery. Most adenoviruses used for gene therapy have been based on serotype 5 (Ad5). Unfortunately, recent data suggest that the primary receptor, the coxsackie-adenovirus receptor (CAR) expression in tumors may be highly variable resulting in resistance to adenovirus infection. Consequently, various strategies have been evaluated to modify adenovirus tropism in order to circumvent CAR deficiency, including retargeting complexes or genetic capsid modifications. To further improve tumor penetration and local amplification of the anti-tumor effect, selectively oncolytic agents, e.g. conditionally replicating adenoviruses (CRAds), have been constructed. Infection of tumor cells results in replication, oncolysis, and subsequent release of the virus progeny. Normal tissue is spared due to lack of replication. This review will focus on a discussion of various modifications of adenovirus to achieve efficient anti-tumor effect, and special emphasis will be placed on CRAds in multimodality treatments.",
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    Adenoviruses for treatment of cancer. / Kanerva, Anna; Hemminki, Akseli.

    In: Annals of Medicine, Vol. 37, 2005, p. 33-43.

    Research output: Contribution to journalArticleScientificpeer-review

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    AB - Most cases of cancer, when detected at an advanced stage, cannot be cured with conventional therapeutic modalities. Therefore, novel targeted approaches such as gene therapy are needed. Nevertheless, while the safety record of gene therapy for cancer has been excellent with more than a thousand patients treated without mortality related to the therapy, clinical efficacy has so far been limited. Moreover, it has become evident that clinical efficacy is partly determined by efficacy of gene delivery. Most adenoviruses used for gene therapy have been based on serotype 5 (Ad5). Unfortunately, recent data suggest that the primary receptor, the coxsackie-adenovirus receptor (CAR) expression in tumors may be highly variable resulting in resistance to adenovirus infection. Consequently, various strategies have been evaluated to modify adenovirus tropism in order to circumvent CAR deficiency, including retargeting complexes or genetic capsid modifications. To further improve tumor penetration and local amplification of the anti-tumor effect, selectively oncolytic agents, e.g. conditionally replicating adenoviruses (CRAds), have been constructed. Infection of tumor cells results in replication, oncolysis, and subsequent release of the virus progeny. Normal tissue is spared due to lack of replication. This review will focus on a discussion of various modifications of adenovirus to achieve efficient anti-tumor effect, and special emphasis will be placed on CRAds in multimodality treatments.

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