Interferons (IFNs) are well-known immunostimulants involved in both innate and adaptive immune responses. These multifunctional proteins mediate an early antiviral response and have pronounced immunomodulatory and antiproliferative properties. Due to their potency, IFNs have been used not only in the treatment of viral infections but also various other diseases. However, the use of IFNs in antitumor therapy has been limited by the frequent severe side effects, which reduced their appeal for the treatment of cancer. In this review, we focused on current data on recombinant IFNs used for anticancer therapy, as well as the development of promising IFN-based gene therapy approaches, with a focus on their safety and therapeutic efficacy. We also highlighted various types of IFNs and their application niches in the treatment of not only cancers in combination therapy but also of certain rare diseases. Taken together, this review improves our understanding of the existing IFN applications in cancer therapy, the disadvantages of using IFNs, and possible approaches for their improvement.

The unique ability of oncolytic viruses (OVs) to replicate in and destroy malignant cells while leaving healthy cells intact and activating the host immune response makes them powerful targeted anti-cancer therapeutic agents. Vesicular stomatitis virus (VSV) only causes mild and asymptomatic infection, lacks pre-existing immunity, can be genetically engineered for enhanced efficiency and improved safety, and has a broad cell tropism. VSV can facilitate targeted delivery of immunostimulatory cytokines for an enhanced immune response against cancer cells, thus decreasing the possible toxicity frequently observed as a result of systemic delivery. In this study, the oncolytic potency of the two rVSV versions, rVSV-dM51-GFP, delivering green fluorescent protein (GFP), and rVSV-dM51-mIL12-mGMCSF, delivering mouse interleukin-12 (mIL-12) and granulocyte-macrophage colony-stimulating factor (mGMCSF), was compared on the four murine cancer cell lines of different origin and healthy mesenchymal stem cells (MSCs) at 24 h post-infection by flow cytometry. Lewis lung carcinoma (LL/2) cells were demonstrated to be more susceptible to the lytic effects of both rVSV versions compared to melanoma (B16-F10) cells. Detection of expression levels of antiviral and pro-apoptotic genes in response to the rVSV-dM51-GFP infection by quantitative PCR (qPCR) showed lower levels of IFIT, RIG-I, and N-cadherin and higher levels of IFNβ and p53 in LL/2 cells. Subsequently, C57BL/6 mice, infused subcutaneously with the LL/2 cells, were injected intratumorally with the rVSV-dM51-mIL12-mGMCSF 7 days later to assess the synergistic effect of rVSV and immunostimulatory factors. The in vivo study demonstrated that treatment with two rVSV-dM51-mIL12-mGMCSF doses 3 days apart resulted in a tumor growth inhibition index (TGII) of over 50%.

Cancer is one of the leading causes of death worldwide. Traditional cancer treatments include surgery, radiotherapy, and chemotherapy, as well as combinations of these treatments. Despite significant advances in these fields, the search for innovative ways to treat malignant tumors, including the application of oncolytic viruses, remains relevant. One such virus is the vesicular stomatitis virus (VSV), which possess a number of useful oncolytic properties. However, VSV-based drugs are still in their infancy and are yet to be approved for clinical use. This review discusses the mechanisms of oncogenesis, the antiviral response of tumor and normal cells, and markers of tumor cell resistance to VSV virotherapy. In addition, it examines methods for producing and arming recombinant VSV and provides examples of clinical trials. The data presented will allow better assessment of the prospects of using VSV as an oncolytic.

The search for effective anti-cancer therapies is one of the most significant goals of modern medicine. The combination of oncolytic viruses (OV) and mRNA immunoadjuvants can significantly improve the outcome or even substitute traditional immunotherapy. In addition to the direct OV-mediated cytotoxic elimination of tumor cells, both OV and mRNA immunoadjuvants can significantly alter the immunosuppressive tumor microenvironment (TME) supporting cancer cells and unleash the immune response against the malignant cells. The present study is aimed at assessing the therapeutic effects of recombinant vesicular stomatitis virus (rVSV) and lipid nanoparticles (LNP) delivering mRNA coding for murine interleukin-12 (mIL12) and granulocyte-macrophage colony-stimulating factor (mGMCSF) (mRNA-LNP) in colorectal carcinoma CT26-induced tumors both as independent therapies and in combination with each other. The results of the in vivo experiment on BALB/c mice demonstrated that rVSV monotherapy did not have a significant effect, with the tumor growth inhibition index (TGII) ranging from 13.7 to 29.8% on days 6–10 after the therapy start. While monotherapy with mRNA-LNP was more effective (TGII of 48.6–53.7%), it was the therapy combining the two approaches (rVSV and mRNA-LNP) that resulted in the highest TGII of 66.7% on day 10. While these results can be further improved by optimizing the experimental design, they show the great potential of combination immunotherapy for the treatment of oncological diseases.