Oncolytic Viruses: New Cancer Immunotherapy Drugs

A special issue of Pharmaceuticals (ISSN 1424-8247). This special issue belongs to the section "Pharmacology".

Deadline for manuscript submissions: 25 August 2024 | Viewed by 2454

Special Issue Editor


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Guest Editor
The Ottawa Hospital Research Institute, Biotherapeutics Manufacturing Centre, Virus Manufacturing Facility, Ottawa, Canada
Interests: oncolytic virotherapy; immunology; immunotherapy; viral vectors

Special Issue Information

Dear Colleagues,

The COVID-19 pandemic has illuminated the power, speed, and adaptability of one of our oldest foes—viruses. Despite the devastating impact of these pathogens, we have been able to harness their abilities to our own advantage and to make them our allies in the fight against the deadly disease that is cancer. The introduction of more advanced gene-editing methods combined with an ever-increasing understanding of both tumor immunology and virology facilitated the development of a new class of anti-cancer therapeutics, known as oncolytic viruses. Despite their name, these viruses do not rely solely on their lytic potential. Several years of research have shown that the interplay of these recombinant viruses and the tumor-microenvironment is much more complex than we initially thought. Instead of being a purely lytic agent, oncolytic viruses can act more as immune modulators, alerting the patient’s immune system to the presence of malignant neoplasms, and thus are able to turn the infamous immunologically “cold” tumor microenvironment into a “hot” one. This can be achieved by clever design and by combining findings from the fields of oncology, immunology, and virology. Research groups around the world are developing novel, advanced, and modified virus platforms, encoding arrays of heterologous proteins and non-coding RNAs, often in combination with modulated expression systems. Combined with a wide variety of available oncolytic virus platforms, originating from the families of Adenoviruses, Herpesviruses, Poxviruses, Rhabdoviruses, and Paramyxoviruses, to name a few, there is an almost infinite field of research on this family of anti-cancer immunotherapy drugs. It is with great pleasure that we showcase a small selection of these advanced technologies developed in this Special Issue on oncolytic viruses.

Dr. Nikolas T. Martin
Guest Editor

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Published Papers (2 papers)

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Article
Cytocidal Effect of Irradiation on Gastric Cancer Cells Infected with a Recombinant Mammalian Orthoreovirus Expressing a Membrane-Targeted KillerRed
by Yoshinori Shirasaka, Kentaro Yamada, Tsuyoshi Etoh, Kazuko Noguchi, Takumi Hasegawa, Katsuhiro Ogawa, Takeshi Kobayashi, Akira Nishizono and Masafumi Inomata
Pharmaceuticals 2024, 17(1), 79; https://doi.org/10.3390/ph17010079 - 8 Jan 2024
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Abstract
The outcomes of unresectable gastric cancer (GC) are unfavorable even with chemotherapy; therefore, a new treatment modality is required. The combination of an oncolytic virus and photodynamic therapy can be one of the promising modalities to overcome this. Mammalian orthoreovirus (MRV) is an [...] Read more.
The outcomes of unresectable gastric cancer (GC) are unfavorable even with chemotherapy; therefore, a new treatment modality is required. The combination of an oncolytic virus and photodynamic therapy can be one of the promising modalities to overcome this. Mammalian orthoreovirus (MRV) is an oncolytic virus that has been used in clinical trials for several cancers. In this study, we developed and evaluated a recombinant MRV strain type 3 Dearing (T3D) that expresses membrane-targeting KillerRed (KRmem), a phototoxic fluorescent protein that produces cytotoxic reactive oxygen species upon light irradiation. KRmem was fused in-frame to the 3′ end of the σ2 viral gene in the S2 segment using a 2A peptide linker, enabling the expression of multiple proteins from a single transcript. RNA electrophoresis, Western blotting, and immunofluorescence analyses confirmed functional insertion of KRmem into the recombinant virus. The growth activity of the recombinant virus was comparable to that of the wild-type MRV in a cultured cell line. The recombinant virus infected two GC cell lines (MKN45P and MKN7), and a significant cytocidal effect was observed in MKN45P cells infected with the recombinant virus after light irradiation. Thus, recombinant MRV-expressing KRmem has the potential to serve as a novel treatment tool for GC. Full article
(This article belongs to the Special Issue Oncolytic Viruses: New Cancer Immunotherapy Drugs)
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Review
Where Are We Now with Oncolytic Viruses in Melanoma and Nonmelanoma Skin Malignancies?
by George Nassief, Angela Anaeme, Karen Moussa, David Chen and George Ansstas
Pharmaceuticals 2024, 17(7), 916; https://doi.org/10.3390/ph17070916 - 9 Jul 2024
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Abstract
Skin cancer prognosis has greatly improved recently due to the introduction of immune checkpoint inhibitors (ICIs). However, many patients with advanced skin cancer still experience immunotherapy resistance and disease progression during ICI treatment, thus calling for novel therapeutics which address this treatment gap. [...] Read more.
Skin cancer prognosis has greatly improved recently due to the introduction of immune checkpoint inhibitors (ICIs). However, many patients with advanced skin cancer still experience immunotherapy resistance and disease progression during ICI treatment, thus calling for novel therapeutics which address this treatment gap. Talimogene laherparepvec (T-VEC) has gained popularity in recent years as a viable treatment option for patients with skin cancer. In preclinical studies, T-VEC demonstrated both a direct anti-tumor effect in injected lesions as well as a systemic immune-mediated effect in non-injected lesions, which could pose additional benefits when combined with ICI therapy. Following promising results from the OPTiM trial, the Food and Drug Administration (FDA) approved the usage of T-VEC as a single agent in advanced melanoma. However, the MASTERKEY-265 trial demonstrated that adding T-VEC to pembrolizumab did not offer additional clinical benefit in patients with melanoma. Nevertheless, the promising efficacy of T-VEC and its approval by the FDA helped oncolytic viruses (OVs) gain wide attention in cancer therapy, and extensive research has been undertaken to evaluate the usage of OVs in other tumors such as sarcomas and breast cancers. Here, we provide a review of clinical results from 2022 to 2024 that investigate the efficacy and safety of OVs as a monotherapy or in combination with other therapies in skin malignancies. Furthermore, we delineate the current limitations in OV utilization and outline future directions to enhance clinical outcomes for patients with skin malignancies receiving OV-based therapies. Full article
(This article belongs to the Special Issue Oncolytic Viruses: New Cancer Immunotherapy Drugs)
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