New perspectives in cancer virotherapy: bringing the immune system into play.

International audienceDespite constant advances in medically orientated cancer studies, conventional treatments by surgery, chemotherapy or radiotherapy remain partly ineffective against numerous cancers. Oncolytic virotherapy - the use of replication-competent viruses that specifically target tumor cells - has opened up new perspectives for improved treatment of these pathologies. Certain viruses demonstrate a natural, preferential tropism for tumor cells, while others can be genetically modified to show such an effect. Several of these viruses have already been used in preclinical and clinical trials in different tumor models; these studies have provided encouraging results and, thus, confirm the growing interest presented by this therapeutic strategy. The role of the immune system in the efficacy of cancer virotherapy has been poorly documented for a long time; however, several recent reports have presented evidence of synergistic effects between both direct viral oncolysis and the activation of specific, anti-tumor immune responses. These findings offer an exciting outlook for the future of cancer virotherapy

Viral cancer therapies : are they ready for combination with other immunotherapies ?

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Le vaccin contre la fièvre jaune : un nouveau traitement anti-tumoral ?

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Measles virus induces oncolysis of mesothelioma cells and allows dendritic cells to cross-prime tumor-specific CD8 response.

International audienceDespite conventional medical and surgical treatments, malignant pleural mesothelioma (MPM) remains incurable. Oncovirotherapy (i.e., the use of replication-competent virus for cancer treatment) is currently explored in clinical trials. In this study, we investigated the antineoplastic potential of a new oncolytic viral agent, a live-attenuated measles virus (MV) strain derived from the Edmonston vaccine lineage (Schwarz strain). We evaluated both oncolytic activity and immunoadjuvant properties of the MV vaccine strain on mesothelioma tumor cells. Infectivity, syncytium formation, and cytolytic activity of MV were studied on a panel of mesothelioma cells derived from pleural effusions of MPM patients. We observed that MV infected preferentially MPM cell lines in comparison with nontransformed mesothelial cells, leading to an efficient killing of a significant fraction of tumor cells. A cytoreductive activity was also evidenced through formation of multinuclear cellular aggregates (syncytia). The susceptibility of MPM cell lines to measles infection was assessed by the analysis of cell surface expression of the MV vaccine receptor (CD46). We also evaluated whether MV infection of mesothelioma cells could elicit an autologous antitumor immune response. We showed that MV Schwarz strain induced apoptotic cell death of infected mesothelioma cells, which were efficiently phagocytosed by dendritic cells (DC). Loading of DCs with MV-infected MPM cells induced DC spontaneous maturation, as evidenced by the increased expression of MHC and costimulatory molecules along with the production of proinflammatory cytokines. Priming of autologous T cells by DCs loaded with MV-infected MPM cells led to a significant proliferation of tumor-specific CD8 T cells. Altogether, these data strongly support the potential of oncolytic MV as an efficient therapeutic agent for mesothelioma cancer

Delivery of cancer therapies by synthetic and bio-inspired nanovectors

International audienceBackground: As a complement to the clinical development of new anticancer molecules, innovations in therapeutic vectorization aim at solving issues related to tumor specificity and associated toxicities. Nanomedicine is a rapidly evolving field that offers various solutions to increase clinical efficacy and safety. Main: Here are presented the recent advances for different types of nanovectors of chemical and biological nature, to identify the best suited for translational research projects. These nanovectors include different types of chemically engineered nanoparticles that now come in many different flavors of 'smart' drug delivery systems. Alternatives with enhanced biocompatibility and a better adaptability to new types of therapeutic molecules are the cell-derived extracellular vesicles and microorganism derived oncolytic viruses, virus-like particles and bacterial minicells. In the first part of the review, we describe their main physical, chemical and biological properties and their potential for personalized modifications. The second part focuses on presenting the recent literature on the use of the different families of nanovectors to deliver anticancer molecules for chemotherapy, radiotherapy, nucleic acid-based therapy, modulation of the tumor microenvironment and immunotherapy. Conclusion: This review will help the readers to better appreciate the complexity of available nanovectors and to identify the most fitting "type" for efficient and specific delivery of diverse anticancer therapies

A Functional Assay to Determine the Capacity of Oncolytic Viruses to Induce Immunogenic Tumor Cell Death

International audienceOncolytic immunotherapy efficacy relies partially on the induction of immunogenic tumor cell death following infection with oncolytic viruses (OV) to induce an antitumor immune response. Here, we describe a method to determine if an OV is able to induce such an immunogenic tumor cell death. This method consists in testing whether tumor cells lysed by an OV are able to induce the maturation of human monocyte-derived immature dendritic cells (Mo-iDC)

Induction of Immunogenic Tumor Cell Death by Attenuated Oncolytic Measles Virus

International audienceAntitumor virotherapy is a developing approach to treat cancer with oncolytic viruses, namely replicative viruses that exclusively or preferentially infect and kill tumor cells. Attenuated strains of Measles Virus (MV) are now being used as oncolytic viruses in clinical trials to treat several types of cancer. The efficacy of oncolytic viruses is mainly due to their capacity to infect and kill tumor cells, but it has also been demonstrated that their capacity to induce immunogenic cell death can activate an antitumor immune response. In this review, we describe the oncolytic capacity of MV and the concept of Immunogenic Cell Death (ICD). We then review how MV induces immunogenic cell death, which can be beneficial for cancer treatment

Oncolytic Virotherapy for human malignant mesothelioma: recent advances

International audienceCancer virotherapy is an attractive alternative to conventional treatments because it offers a wide range of antitumor effects due to 1) the diversity of the oncolytic viruses that are now available and 2) their multifaceted activities against both tumor cells and tumor vessels, in addition to their ability to induce antitumor immune responses. In this review, we summarize preclinical and clinical data regarding the targeting of malignant mesothelioma (MM) by oncolytic viruses. We also discuss the potential of other oncolytic viruses that have already shown antitumor effects against several malignancies in advanced clinical trials but are yet to be tested against MM cells. Finally, we review how the activation of the immune system and combinations with other types of anticancer treatments could support the development of oncolytic virotherapy for the treatment of MM