Chitosan-Based Nanoparticles for Intracellular Delivery of ISAV Fusion Protein cDNA into Melanoma Cells: A Path to Develop Oncolytic Anticancer Therapies.

Claudia Robles-Planells,Ricardo Fernandez,Marcelo J Kogan,Luis A Milla,Claudio Acuña-Castillo,Silvia Matiacevich,Edison Salas-Huenuleo,Carlos Barrera-Avalos,Juan Pablo Huidobro-Toro,Giselle Sánchez-Guerrero,Eugenio Spencer,Jorge Pavez,Mónica Imarai,Alejandro Escobar,Leonel E Rojo

doi:10.1155/2020/8680692

Abstract

Oncolytic virus therapy has been tested against cancer in preclinical models and clinical assays. Current evidence shows that viruses induce cytopathic effects associated with fusogenic protein-mediated syncytium formation and immunogenic cell death of eukaryotic cells. We have previously demonstrated that tumor cell bodies generated from cells expressing the fusogenic protein of the infectious salmon anemia virus (ISAV-F) enhance crosspriming and display prophylactic antitumor activity against melanoma tumors. In this work, we evaluated the effects of the expression of ISAV-F on the B16 melanoma model, both in vitro and in vivo, using chitosan nanoparticles as transfection vehicle. We confirmed that the transfection of B16 tumor cells with chitosan nanoparticles (NP-ISAV) allows the expression of a fusogenically active ISAV-F protein and decreases cell viability because of syncytium formation in vitro. However, the in vivo transfection induces a delay in tumor growth, without inducing changes on the lymphoid populations in the tumor and the spleen. Altogether, our observations show that expression of ISAV fusion protein using chitosan nanoparticles induces cell fusion in melanoma cells and slight antitumor response.

Highlights

Oncolytic virus therapy is an emerging promissory option for cancer treatment
Syncytium is viable for short time periods, and evidence suggests that it undergoes immunogenic cell death (ICD) [3]
We evaluated a new transfection strategy based on chitosan nanoparticles for in situ transfections of murine melanoma tumors with the ISAV fusion protein gene

Summary

Introduction

Oncolytic virus therapy is an emerging promissory option for cancer treatment. It uses competent replicating viruses as tools to destroy cancer cells. The ability to efficiently induce cellular destruction in tumor cells is associated with impaired genome repairing mechanisms, which allow unregulated viral replication, as well as alteration of immune response mechanisms [1] In normal cells, these protective responses keep viral replication under control, but fusogenic oncolytic viruses waive these protective responses, and this is why they are considered promising candidates to enhance immunotherapy and initiate broad antitumor responses. Additional oncolytic viruses and their uses in combination with other treatments are currently under investigation [5]; several of them are already at the level of clinical trials with promising effects [3, 6] Some of these viruses promote efficient malignant cell death, employing direct and/or immune-mediated mechanisms [7, 8]

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