Virologie最新文献

Despite advances in research and clinical practice, pancreatic ductal adenocarcinoma remains a major public health challenge due to the lack of early detection and effective treatments. In this context, oncolytic viruses have emerged as a promising therapeutic alternative. These viruses selectively infect and lyse cancer cells after replication while also having the potential to induce an antitumor immune response. This review explores the fundamental aspects of pancreatic cancer and its management, along with the principles of oncolytic virotherapy, highlighting clinically used viruses before discussing the therapeutic potential of the SG33 myxoma virus strain in pancreatic cancer virotherapy.

Antitumor immuno-virotherapy involves the use of replicating oncolytic viruses capable of selectively infecting and killing tumor cells, with the aim of stimulating an antitumor immune response. Attenuated strains of measles virus (MeV) used as measles vaccines are good candidates. Attenuated MeVs use the CD46 molecule as a tumor cell entry receptor, but also CD150/SLAM and Nectin-4. The CD46 molecule blocks complement-mediated lysis and is frequently overexpressed by many cancer cell types, enabling the attenuated MeV to infect these cells. In addition, MeVs take advantage of defects in the antiviral type I interferon (IFN I) response in tumor cells to replicate, while this antiviral response blocks its replication in healthy cells. Attenuated MeVs display oncolytic properties against numerous cancers in vitro and in mouse models. They induce immunogenic cell death with infiltration of tumors by immune cells, notably T lymphocytes, thus activating the anti-tumor immune response. Several phase I and II clinical trials using different MeVs have been carried out, with encouraging results. Here, we provide an update on this therapeutic approach.

Among the wide range of viruses studied for their possible use as an oncolytic virus, the mammalian reovirus has the particularity of being naturally oncolytic, without requiring prior genetic modification. Since the 1970s, it has been observed that this virus has a propensity to destroy transformed cells in a preferential manner. These preliminary observations were refined at the end of the 1990s, and the idea of using reovirus as an oncolytic virus in anticancer virotherapy quickly took hold. This review briefly describes the main steps of the viral replication cycle pertinent to the oncolytic activity of the virus, as well as possible strategies for better optimization of this activity.

Among the wide range of viruses studied for their possible use as an oncolytic virus, the mammalian reovirus has the particularity of being naturally oncolytic, without requiring prior genetic modification. Since the 1970s, it has been observed that this virus has a propensity to destroy transformed cells in a preferential manner. These preliminary observations were refined at the end of the 1990s, and the idea of using reovirus as an oncolytic virus in anticancer virotherapy quickly took hold. This review briefly describes the main steps of the viral replication cycle pertinent to the oncolytic activity of the virus, as well as possible strategies for better optimization of this activity.

Current treatments against the hepatitis B virus (HBV) efficiently inhibit viral replication but rarely lead to functional cure, defined as the loss of HBsAg. Persisting transcription from intranuclear forms of viral DNA, independently from viral replication, limits the possibility of a robust clearing response of the host against the virus. The new therapeutic approaches target either the transcription, with specific oligonucleotides, the capsid assembly or the release of complete viral particles from infected hepatocytes. Some clinical trials seem highly promising. Although the clinical evolution of hepatitis Delta infection is more severe than the one caused by HBV, our tools to fight the virus are even less developed. In addition to the strategies used for HBV, molecules targeting HDV entry or HDAg prenylation are currently being evaluated. We review the main characteristics of HBV and HDV viral replication and highlight the results obtained in clinical trials using the most advanced molecules developed to overcome these infections.