Special Issue "Gene Therapy Used in Cancer Treatment"
A special issue of Biomedicines (ISSN 2227-9059).
Deadline for manuscript submissions: 31 December 2013
Dr. Vincenzo Cerullo
Laboratory of Immunovirotherapy Division of Biopharmaceuthics and Pharmacokinetics, Faculty of Pharmacy University of Helsinki, Helsinki, Finland
Phone: +358 9 191 59156
Interests: gene therapy; cancer gene therapy; immunotherapy; immunity; innate immunity; immunovirotherapy; oncolytic viruses; adenovirus; vaccinia virus
This special issue "Gene Therapy for Cancer Treatment" will be mainly focused on the different aspects of cancer gene therapy, gene immunotherapy and immunovirotherapy.
For long time the term "Cancer Gene Therapy" has been mostly referred to oncolytic viruses or viral vector expressing anti-tumor molecules, leaving aside immunotherapy approaches. Nowadays several studies have highlighted the capacity of viral and non-viral approaches to "turn-on" the immune system and the use of this feature to further potentiate the efficacy of the treatment.
More specifically, in this issue papers can be focused on viral and non-viral approaches to cancer therapy, their use as immunotherapy platforms, their modification to increase the safety and/or immunogenicity. Both preclinical and clinical studies will be considered.
Dr. Vincenzo Cerullo
Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. Papers will be published continuously (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.
Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are refereed through a peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Biomedicines is an international peer-reviewed Open Access quarterly journal published by MDPI.
Please visit the Instructions for Authors page before submitting a manuscript. For the first couple of issues the Article Processing Charge (APC) will be waived for well-prepared manuscripts. English correction and/or formatting fees of 250 CHF (Swiss Francs) will be charged in certain cases for those articles accepted for publication that require extensive additional formatting and/or English corrections.
- gene therapy
- cancer gene therapy
- oncolytic viruses
- cancer vaccines
The below list represents only planned manuscripts. Some of these manuscripts have not been received by the Editorial Office yet. Papers submitted to MDPI journals are subject to peer-review.
Type of Paper: Article
Title: Hepatocyte Gene Therapy
Authors: Pasquale Piccolo 1 and Nicola Brunetti-Pierri 1,2
1 Telethon Institute of Genetics and Medicine (TIGEM), Naples, Italy
2 Department of Translational Medicine, Federico II University of Naples, Naples, Italy
Abstract: Recombinant adenoviruses (Ad) are among the most extensively used vectors for liver-directed gene transfer. Helper-dependent adenoviral (HDAd) vectors that are devoid of all viral coding sequences are particularly promising non-integrating vectors for liver directed gene therapy because they efficiently transduce hepatocytes, have a large cloning capacity, and can result in long-term transgene expression without chronic toxicity. The main obstacle preventing clinical applications of HDAd for liver-directed gene therapy is the host innate inflammatory response against the vector capsid proteins that occurs shortly after intravascular vector administration resulting in acute toxicity, the severity of which is dependent on vector dose. Intense efforts have been focused on elucidating the factors involved in this acute response and various strategies have been investigated to improve the therapeutic index of HDAd vectors. These strategies have yielded encouraging results with the potential for clinical translation for therapy of inborn errors of metabolism and cancer.
Keywords: Adenovirus; helper-dependent adenoviral vectors; gutless vectors; liver directed gene therapy
Type of Paper: Article
Title: Gene transfer of gulonolactone oxidase into human hepatocellular carcinoma cells with gulonolactone treatment restores some ascorbate biosynthesis and reduces hypoxia inducible factor 1
Authors: Teresa Flett, Elizabeth Campbell, Elisabeth Phillips, Margreet CM Vissers and Gabi U Dachs*
Affiliation: Mackenzie Cancer Research Group, and Centre for Free Radical Research, Department of Pathology, University of Otago, Christchurch, New Zealand
Abstract: Humans are unable to synthesise ascorbate (vitamin C) due to a non-functional gulonolactone oxidase (Gulo) enzyme. Ascorbate is a vital micronutrient required for many biological functions, including its action as a cofactor for metalloenzymes. As enzyme cofactor, it is important for the regulation of hypoxia-inducible factor-1 (HIF-1), which governs cancer growth and spread. This study aimed to restore ascorbate synthesis to human cells and to determine the effect of ascorbate biosynthesis on HIF-1 levels. HepG2 cells were gene modified with a plasmid encoding the mouse Gulo cDNA and tested for genomic incorporation by PCR, and ascorbate synthesis by high performance liquid chromatography. A PCR-positive stable clone was able to synthesise ascorbate but only when gulonolactone was supplied. Intracellular ascorbate concentrations reached 5% of saturation levels. Addition of gulonolactone to this clone reduced hypoxic HIF-1 induction.
Type of Paper: Review
Title: Application of helper-dependent adenoviral vector for cancer immunotherapy
Author: Masataka Suzuki
Affiliation: Department of Medicine, Center for Cell and Gene Therapy, Baylor College of Medicine, 1102 Bates Ave., Ste. 1770, Houston Texas 77030, USA
Abstract: Helper-dependent adenoviral vectors (HDAds), devoid of viral coding sequences, allow for insertion of large or multiple transgenes in a single vector and have been primarily studied for application to genetic disorders. However, clinical application of HDAds for genetic disorders has been hampered by an acute toxic response. However, this obstacle for gene replacement therapy could be strategically advantageous for the activation of an immune response as an adjunct treatment in cancer. Cancer treatments including immunotherapy are frequently limited by the inhibitory environment produced by both tumors and their stroma, both of which express numerous inhibitory molecules. Hence these multiple inhibitory mechanisms must be overcome for development of anti-tumor immunity. A major attribute of HDAds is their large coding capacity that can accommodate multiple immune modulating transgenes that could produce a combined effect to overcome tumor-derived inhibition and ensure intratumoral effector T cell proliferation and function. In this review, we discuss the advantages of an application of HDAds to cancer immunotherapy.
Type of Paper: Review
Authors: Markus Vähä-Koskela 1, Ari Hinkkanen 2
Affiliations: 1. Institute of Biotechnology, University of Helsinki, Finland
2. A.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Kuopio, Finland
Abstract: One severe obstacle in oncolytic virotherapy is an in vivo resistance to virus of the tumors. Several recent studies show that the high therapeutic efficacy observed for some oncolytic vehicles is based on rapid high blood viremia upon systemic virus administration, a crucial feature for efficient targeting of invasive and metastatic tumors. Yet, use of xenografts may be delivering partial information while mice are lacking functional immune system. For example complete eradication of intracranial U87 human glioma xenografts in mice was achieved upon peripheral SFV VA7 alphavirus administration, but in sharp contrast, mouse syngeneic GL261, CT-2A and DBT gliomas proved completely resistant to VA7 infection in vivo and could be ascribed robust antiviral type I interferon response (Ruotsalainen et al., 2012; Vähä-Koskela et al., 2013; Quetglas et al., 2013), virtually absent from U87 model. Similar results weer obtained in studies with SFV by Quetglas et al., (2013) and by Escobar-Zarate et al. for VSV infection of solid tumors (2013), who noticed that positive therapy response was inversely correlated to activation status of interferon I-dependent JAK/STAT signaling pathway. Therefore, by addressing the mechanisms of resistance to virus using tumor models would reveal cellular targets for intervention. In this paper we discuss the hurdles intracellular immune mechanisms set to viral therapy of tumors and evaluate the strategies to circumvent the resistance to oncolytic virus without compromising safety.
Last update: 22 November 2013