Head and neck cancer cells are efficiently infected by Ad5/35 hybrid virus

Suominen, Elina; Toivonen, Raine; Grénman, Reidar; Savontaus, Mikko

doi:10.1002/jgm.957

Cited by 17 publications

(12 citation statements)

References 36 publications

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“…Serotype 3 uses CD46, CD80 and CD86, and serotype 35 CD46 as their primary cellular receptors (Gaggar et al 2003;Short et al 2004). Extensive data demonstrate that both serotypes are able to efficiently transduce many cell types that are relatively resistant to Ad5 infection, including hematopoetic stem cells, tumor endothelial cells, and several cancer cell types (Amin 2003;Kanerva et al 2002;Segerman et al 2000;Shayakhmetov et al 2002;Shinozaki et al 2006;Sova et al 2004;Suominen et al 2006).…”

Section: Introductionmentioning

confidence: 94%

Dilated cardiomyopathy alters the expression patterns of CAR and other adenoviral receptors in human heart

Toivonen

Mäyränpää

Kovanen

et al. 2009

Histochem Cell Biol

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Gene therapy trials for heart failure have demonstrated the key role of efficient gene transfer in achieving therapeutic efficacy. An attractive approach to improve adenoviral gene transfer is to use alternative virus serotypes with modified tropism. We performed a detailed analysis of cardiac expression of receptors for several adenovirus serotypes with a focus on differential expression of CAR and CD46, as adenoviruses targeting these receptors have been used in various applications. Explanted hearts from patients with DCM and healthy donors were analyzed using Q-RT-PCR, western blot and immunohistochemistry. Q-RT-PCR and Western analyses revealed robust expression of all receptors except CD80 in normal hearts with lower expression levels in DCM. Immunohistochemical analyses demonstrated that CD46 expression was somewhat higher than CAR both in normal and DCM hearts with highest levels of expression in intramyocardial coronary vessels. Total CAR expression was upregulated in DCM. Triple staining on these vessels demonstrated that both CAR and CD46 were confined to the subendothelial layer in normal hearts. The situation was clearly different in DCM, where both CAR and CD46 were expressed by endothelial cells. The induction of expression of CAR and CD46 by endothelial cells in DCM suggests that viruses targeting these receptors could more easily gain entry to heart cells after intravascular administration. This finding thus has potential implications for the development of targeted gene therapy for heart failure.

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Section: Introductionmentioning

confidence: 94%

Dilated cardiomyopathy alters the expression patterns of CAR and other adenoviral receptors in human heart

Toivonen

Mäyränpää

Kovanen

et al. 2009

Histochem Cell Biol

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“…CD46-binding adenoviruses might also deliver therapeutic tumor-suppressing genes (e.g. p53) to cancer cells [57].…”

Section: The Usage Of Complement Molecules To Improve Vaccination or mentioning

confidence: 99%

Complement: An Efficient Sword of Innate Immunity

Rambach¹,

Würzner²,

Speth³

2008

Contributions to Microbiology

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Complement is vital for protecting individuals against pathogens and any disturbance of homeostasis associated with appearance of foreign antigens. Four antenna molecules seek for putative danger and subsequently start three activation pathways to eliminate the hostile triggering signal. To achieve this mission the complement arsenal contains soluble plasma factors as well as membrane-bound receptor molecules. Fulfilling a broad spectrum of biological functions, complement participates to construct and orchestrate an immunological network with extensive links to other elements of innate immunity, but also to its younger brother, the adaptive immune system. The body generously supports the complement activity with a high level of complement production; not only the liver as 'the capital of complement expression' but also decentralized synthesis sites guarantee its all-over presence. On the other hand, it is of fundamental interest for the organism to limit this powerful immunological regiment by establishing a tight surveillance composed of redundantly acting regulator molecules. To find the appropriate dimension of complement activity is critical, as shown by the spectrum of diseases associated with an excess or a lack. Numerous therapeutic approaches aim to correct such an imbalance and to re-establish the antimicrobial capacity of complement without induction of chronic inflammation and autoimmunity.

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“…The coxsackie and adenovirus receptor (CAR) is the primary receptor for adenovirus type 5; however, it is expressed at low and often variable levels in HNSCCs [30, 31]. Furthermore, the levels of CAR expression have also been shown to decrease with the malignant progression of HNSCCs [32].…”

Section: Discussionmentioning

confidence: 99%

Oncolytic adenoviruses targeted to Human Papilloma Virus-positive head and neck squamous cell carcinomas

et al. 2016

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Objectives In recent years, the incidence of Human Papilloma Virus (HPV)-positive head and neck squamous cell carcinomas (HNSCC) has markedly increased. Our aim was to design a novel therapeutic agent through the use of conditionally replicative adenoviruses (CRAds) that are targeted to the HPV E6 and E7 oncoproteins. Methods Each adenovirus included small deletion(s) in the E1a region of the genome (Δ24 or CB016) intended to allow for selective replication in HPV-positive cells. In vitro assays were performed to analyze the transduction efficiency of the vectors and the cell viability following viral infection. Then, the UPCI SCC 090 cell line (HPV-positive) was used to establish subcutaneous tumors in the flanks of nude mice. The tumors were then treated with either one dose of the virus or four doses (injected every fourth day). Results The transduction analysis with luciferase-expressing viruses demonstrated that the 5/3 fiber modification maximized virus infectivity. In vitro, both viruses (5/3Δ24 and 5/3CB016) demonstrated profound oncolytic effects. The 5/3CB016 virus was selective for only HPV-positive HNSCC cells, whereas the 5/3Δ24 virus killed HNSCC cells regardless of HPV status. In vivo, single injections of both viruses demonstrated anti-tumor effects until only 6–8 days following viral inoculation. However, after four viral injections, there was statistically significant reduction in tumor growth when compared to the control group (p<0.05). Conclusion CRAds targeted to HPV-positive HNSCCs demonstrated excellent in vitro and in vivo therapeutic effects, and they have the potential to be clinically translated as a novel treatment modality for this emerging disease.

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Head and neck cancer cells are efficiently infected by Ad5/35 hybrid virus

Cited by 17 publications

References 36 publications

Dilated cardiomyopathy alters the expression patterns of CAR and other adenoviral receptors in human heart

Dilated cardiomyopathy alters the expression patterns of CAR and other adenoviral receptors in human heart

Complement: An Efficient Sword of Innate Immunity

Oncolytic adenoviruses targeted to Human Papilloma Virus-positive head and neck squamous cell carcinomas

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