Studies on the use of viruses in the treatment of carcinoma of the cervix

Smith, Robert R.; Huebner, Robert J.; Rowe, Wallace P.; Schatten, William E.; Thomas, Louis B.

doi:10.1002/1097-0142(195611/12)9:6<1211::aid-cncr2820090624>3.0.co;2-7

Cited by 274 publications

(94 citation statements)

References 14 publications

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“…4 In light of the findings of this study, it is interesting to note that the potential therapeutic use of wild-type adenoviruses as oncolytic agents was recognized and tested in patients with cervical carcinoma in the early 1950s based on the observation that these viruses replicate efficiently and kill cultured HeLa cells. 20 Such therapies were not pursued aggressively possibly because of the variable responses due to limitations in technologies for the production and purification of viruses and the development of more active chemotherapeutic agents.…”

Section: Discussionmentioning

confidence: 99%

Inefficient killing of quiescent human epithelial cells by replicating adenoviruses: potential implications for their use as oncolytic agents

Vaillancourt¹,

Atencio²,

Quijano³

et al. 2005

Cancer Gene Ther

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Cultured primary human cells have been widely used to assess the selectivity of oncolytic viruses as potential anticancer agents. As culture conditions can potentially have a significant impact on virus replication and ultimately cell killing, we evaluated the effects of dl309, a wild-type adenovirus, and dl01/07, a conditionally replicating adenovirus mutant, on quiescent and proliferating primary mammary epithelial cells. When primary cells were induced into quiescence, both viruses exhibited similar attenuated cell killing. However, cell killing by dl309 was superior to dl01/07 in proliferating primary cells. Analysis of viral effects at the level of entry, E2F activation, DNA replication, and late gene expression indicated that attenuation of dl309 in quiescent cells correlated with decreased expression of viral late genes such as hexon. In contrast, attenuation of dl01/07 in quiescent cells correlated with inefficient induction of E2F activity and inability to undergo efficient DNA replication. In proliferating cells, dl309 replicated efficiently, whereas dl01/07 still showed attenuated replication. In summary, our results indicate the intrinsic preference of wildtype adenoviruses for killing proliferating cells, which is an attractive feature for using adenoviruses as oncolytic agents. These results also highlight the need for the use of appropriate growth conditions for primary cells in vitro to distinguish subtle differences in cell killing among various oncolytic viruses. Cancer Gene Therapy (2005) R eplication-competent adenoviruses are currently being evaluated as novel anticancer agents. A number of modifications in the genome of the adenovirus have been reported to result in viruses that are capable of selectively replicating in and killing cancer cells. 1,2 Based on their ability to selectively kill tumor cells in cell culture and antitumor activity in xenograft tumor models, a few of these engineered viruses are currently being evaluated as oncolytic agents in the clinic. 3 As human adenoviruses do not replicate well in nonhuman cells, it has not been possible to study toxicity related to replication in nontarget tissues in preclinical animal models. In the absence of suitable in vivo models, analysis of selective replication is widely performed by studying these viruses for their effect in vitro on tumor cells lines and primary nontransformed cells. 4 The effect of oncolytic viruses in vitro has been determined at the level of viral DNA replication, late gene expression, induction of cell death, and production of progeny virion. 5 In the in vitro assays, whether cells are rapidly growing or arrested can potentially have a significant effect on virus replication and ultimately cell killing.In the present study, we sought to compare the effect of the wild-type adenovirus and a mutant that was previously reported to replicate preferentially in tumor cells for their effects in proliferating and quiescent normal cells. Our results show that in vitro, replication competent adenoviruses including wild ...

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Section: Discussionmentioning

confidence: 99%

Inefficient killing of quiescent human epithelial cells by replicating adenoviruses: potential implications for their use as oncolytic agents

Vaillancourt¹,

Atencio²,

Quijano³

et al. 2005

Cancer Gene Ther

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show abstract

“…6,7 In the 1950s and 1960s 'wild-type' replication-competent viruses were used to treat a variety of malignancies via direct intratumoral injection. 8,9 These therapies were abandoned due to limited responses and the development of better chemotherapeutic agents. However, with the recent advances in the development of gene therapy vectors, specifically the ability to intro- showed high level production of the HSVtk transgene and was more efficacious than a non-replicating virus in vitro, after injection into flank tumors, and against established intraperitoneal tumors.…”

Section: Introductionmentioning

confidence: 99%

Inclusion of the herpes simplex thymidine kinase gene in a replicating adenovirus does not augment antitumor efficacy

et al. 2001

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Replication-incompetent adenoviruses (Ad) carrying the herpes simplex thymidine kinase (HSVtk) gene have been used in a number of human cancer gene therapy trials, however transduction has generally been limited to a small minority of tumor cells. To solve this problem, replication-competent adenoviral vectors carrying transgenes such as HSVtk have been developed. However, contradictory evidence exists regarding the efficacy of these new vectors. Accordingly, we constructed and tested a replication-competent E3-deleted adenoviral vector containing the HSVtk suicide gene driven by the endogenous E3 promoter (Ad.wt.tk). This virus

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“…90 Because of high infectivity, cytotoxicity, and immunogenicity, Ad vectors have been very useful in the development of novel anticancer medicines. The application potential of rAd for gene therapy of cancer has been rapidly explored with several strategies.…”

Section: Application Of Ad Vectors In Cancer Treatmentmentioning

confidence: 99%

“…135 The lytic potency of Ad prompted it to be considered as a candidate cancer therapy agent. 90 Wt live human Ads were first tried in the treatment of cervical cancer right after discovery of the viruses in 1953. 136 Large amounts of virus were given to patients through i.t., intra-arterial, or i.v.…”

Section: Application Of Ad Vectors In Cancer Treatmentmentioning

confidence: 99%

“…Autopsy findings confirmed the clinical observations that the injected virus produced only local effects on the cervical tumor and did not affect the progressive growth of tumors in the pelvic tissues or the development and growth of metastases. 90 Two other recent approaches using Ad-based vectors exploited the interaction of AdE1 region proteins with cellular proteins and their ability to induce target cell apoptosis. AdE1A protein has been shown to be able to induce apoptosis in cultured cells.…”

Section: Application Of Ad Vectors In Cancer Treatmentmentioning

confidence: 99%

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Development and application of adenoviral vectors for gene therapy of cancer

Zhang¹

1999

Cancer Gene Ther

165

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For successful gene vaccination and therapy of cancer, it is essential to develop gene delivery vectors that can meet clinical and social requirements. The need for improved vectors was clearly manifested during the peak of the first wave of gene therapy. Adenoviral (Ad) vectors have recently drawn the attention of many of those involved in the field of gene therapy for cancer because of their practical advantages and application potential. Many experiments, innovations, preclinical studies, and clinical trials have generated an overwhelming amount of data and literature concerning this vector system. It is hoped that the comprehensive review presented here, which includes the principles, potential, capacity, and limitations of the current Ad systems, will help to further the rational development of the system. The literature in this article is organized in an attempt to emphasize Ad vector development in the aspects of technical approaches, practical hurdles and strategies to overcome them, significant experimental results, recent advances, future directions, etc. The technical range of this review covers details that are intended to serve as a reference for advanced technical readers and provide a foundation for initiates in the field of Ad vector gene therapy. The material presented here is also intended for nontechnical persons who want to have an overview of the significance and potential of the technology.

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Studies on the use of viruses in the treatment of carcinoma of the cervix

Cited by 274 publications

References 14 publications

Inefficient killing of quiescent human epithelial cells by replicating adenoviruses: potential implications for their use as oncolytic agents

Inefficient killing of quiescent human epithelial cells by replicating adenoviruses: potential implications for their use as oncolytic agents

Inclusion of the herpes simplex thymidine kinase gene in a replicating adenovirus does not augment antitumor efficacy

Development and application of adenoviral vectors for gene therapy of cancer

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