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Review
. 2014 Jan;12(1):23-34.
doi: 10.1038/nrmicro3140. Epub 2013 Dec 2.

New viruses for cancer therapy: meeting clinical needs

Tanner S Miest  1 , Roberto Cattaneo  1
Affiliations
Review

New viruses for cancer therapy: meeting clinical needs

Tanner S Miest et al. Nat Rev Microbiol. 2014 Jan.

Abstract

Early-stage clinical trials of oncolytic virotherapy have reported the safety of several virus platforms, and viruses from three families have progressed to advanced efficacy trials. In addition, preclinical studies have established proof-of-principle for many new genetic engineering strategies. Thus, the virotherapy field now has available a diverse collection of viruses that are equipped to address unmet clinical needs owing to improved systemic administration, greater tumour specificity and enhanced oncolytic efficacy. The current key challenge for the field is to develop viruses that replicate with greater efficiency within tumours while achieving therapeutic synergy with currently available treatments.

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Figures

Figure 1
Figure 1. Vector-shielding strategies
a | Interchange of different serotypes from the same virus species is shown for vesicular stomatitis virus (VSV), which has only one envelope glycoprotein. b | Replacement of multiple immunogenic epitopes in different proteins is shown for adenovirus; exchange can be achieved using full domains (such as the fibre knob) or individual motifs (such as hexon hypervariable loops). c | Generation of a new serotype is shown for measles virus. The two glycoproteins of this monotypic virus are substituted by the glycoproteins of an animal virus of the same genus. d | Chemical shielding of viral epitopes is shown for adenovirus; small polymers can be added to purified viral particles.
Figure 2
Figure 2. Principles of tumour targeting — illustrated for four virus families
From top to bottom: targeting cell entry (detargeting from natural receptors and retargeting to tumour surface markers) and post-entry targeting (targeting of transcription, replication or microRNAs (miRNAs)). CAR, coxsackie–adenovirus receptor; HVEM, herpesvirus entry mediator; SLAM, signalling lymphocytic activation molecule.
Figure 3
Figure 3. Post-entry targeting
a | Positive transcription targeting relies on promoters that are highly expressed in cancer cells to stimulate the preferential expression of viral genes or transgenes in tumours. b | Negative targeting depends on microRNA (miRNA) expression in normal cells to restrict the replication of vectors that express miRNA-recognition sequences within their genomes. Tumours have decreased expression of certain miRNAs, which renders them unable to restrict vector replication.
Figure 4
Figure 4. Arming strategies that induce bystander cell killing
a | Convertase enzymes that are expressed in infected cells metabolize prodrugs into toxic metabolites that diffuse and kill uninfected tumour cells. b | The sodium–iodide symporter (NIS) concentrates radioactive ions in infected cells, which induces radiation poisoning of uninfected bystander tumour cells. c | Immunostimulatory transgenes that are expressed in infected cells prime responses against tumour antigens, which causes the systemic destruction of tumour cells.
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