Immunotherapy is at the cutting edge of modern cancer treatment. Innovative medicines have been developed with varying degrees of success that target all aspects of tumor biology: tumors, niches, and the immune system. Oncolytic viruses (OVs) are a novel and potentially immunotherapeutic approach for cancer treatment. OVs reproduce exclusively in cancer cells, causing the tumor mass to lyse. OVs can also activate the immune system in addition to their primary activity. Tumors create an immunosuppressive environment by suppressing the immune system’s ability to respond to tumor cells. By injecting OVs into the tumor, the immune system is stimulated, allowing it to generate a robust and long-lasting response against the tumor. The essential biological properties of oncolytic viruses, as well as the underlying mechanisms that enable their usage as prospective anticancer medicines, are outlined in this review. We also discuss the increased efficacy of virotherapy when combined with other cancer medications.
Cancer leftovers one of the world’s utmost common causes of mortality. The necessity for novel treatment options is becoming increasingly critical as the global cancer incidence continues to increase. Despite the availability of numerous therapeutic methods for cancer treatment, such as surgery, radiation, and chemodrugs, the risk of recurrence remains significant. Immunotherapeutic approaches for cancer treatment have become increasingly popular in preclinical research and clinical practice over the last decade [1]. Traditional oncological strategies are aimed at removing or killing tumor cells directly.
On the other hand, immunotherapy is performed to improve the immune system’s ability to destroy cancer cells, leading to tumor regression, establishment of antitumor immune memory, and, finally, long-lasting reactions. This can be accomplished through various strategies such as monoclonal antibodies, cancer vaccines, and immune checkpoint inhibitors [2]. It was discovered in the early 1900s that natural viral infection caused tumor regression, which sparked an interest in using viruses to treat cancer. However, because of concerns about viral pathogenicity and toxicity, this technique was ruled out. Oncolytic viruses (OVs) are a new generation of viruses created as a result of recent developments in genetic engineering technologies that assure their safety and potency [3].
Information about the immune response to new or even old viruses is constantly changing and needs to be updated [4], because viruses’ characteristics change due to geographical and natural interactions [5]. Scientists discovered that some viruses could naturally kill tumor cells in the last century. OVs were generated from wild-type or naturally attenuated virus strains during this time, leaving a lot of space for development in terms of safety and antitumor effects. OV-mediated cancer virotherapy has emerged as a new and successful cancer treatment strategy. Many OVs have been used, and numerous viruses have been studied for cancer therapy [6]. OVs are cancer-targeting viruses that can be native or recombinant. The viruses kill cancer cells in their last stages of replication by lysis or by stimulating an antitumor immune reaction, consequently diminishing impairment in healthy organs [7]. The antitumor efficacy of OVs is based on a number of processes that include the natural interactions between viruses, cancer cells, and the immune system. Another benefit of OVs for cancer therapy is that they may be utilized to impress gene expression in the tumor microenvironment, which either enhances the OVs’ ability or boosts the immune system’s antitumor arm [8].
The fundamental knowledge of viruses’ anticancer properties is rapidly converted into feasible therapy alternatives for aggressive cancers, which is a fascinating phase in the evolution of the OV field. The main goal of this review was to evaluate the monotherapy of OVs in comparison with other therapeutic approaches and highlight the importance of combination therapy because of insufficient antitumor response during OV monotherapy. Additionally, we describe how OVs are important in cancer diagnosis and treatment. Also, the synergistic efficacy of OVs in combination with targeted therapy, radiation, chemotherapy, and immunotherapeutic drugs is described in this review.
All data generated or analyzed during this study are included in this published article.
There is no conflict of interest.
All the authors contributed equally.
We thank those who help us in writing this manuscript.
Despite advances in treatment, cancer remains a leading cause of death worldwide. Although treatment strategies are continually progressing, cancers have evolved many mechanisms for evading therapies and the host immune system. Oncolytic viruses (OVs) could provide a much-needed option for cancers that are resistant to existing treatments. OVs can be engineered to specifically target and kill cancer cells, while simultaneously triggering an immune response at the site of infection. This review will focus on the challenges of developing a successful OV and translation to clinical practice, discussing the innovative strategies that are being used to optimize the potential of OVs. Here, we will also explore the current clinical landscape and the prospects of OVs in early clinical development.
Oncolytic viruses (OVs) are viruses that may help destroy tumor cells. They work by selectively infecting and replicating within tumor cells, causing the cells to burst and release newly built viruses. These viruses infect nearby tumor cells, triggering the body's immune system to attack the tumor and any tumor cells that have spread throughout the body. Clinical trials have shown that OVs can destroy cancer cells that are resistant to standard therapies. OVs in combination with other cancer therapies can be more effective and there are over 100 clinical trials planned, ongoing or completed to investigate this approach. OVs are generally well tolerated, the most common treatment-related side effects include fever, aches and pains, and tiredness for 1–2 days. While only four OVs have been approved so far, there are more expected to come. Overall, OVs may provide a way to directly destroy tumors and turn on the immune system to destroy tumor cells throughout the body.
Click to tweetOVs may provide a much-needed option for cancers resistant to existing treatments. This review will explore the challenges of developing a successful OV, current clinical landscape and the prospects of OVs in early clinical development.
The authors meet criteria for authorship as recommended by the International Committee of Medical Journal Editors (ICMJE). Boehringer Ingelheim International GmbH was given the opportunity to review the manuscript for medical and scientific accuracy as well as intellectual property considerations.
UM Lauer has worked as a consultant for Boehringer Ingelheim, ViraTherapeutics and MSD/Themis Bioscience, and as an advisor for Novartis, Amgen and Bayer. J Beil has nothing to declare. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. The authors did not receive payment related to the development of the review.
V Cronin of MediTech Media provided writing and editorial support, which was contracted and funded by Boehringer Ingelheim International GmbH.
This work is licensed under the Attribution-NonCommercial-NoDerivatives 4.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-nd/4.0/
A promising future for oncology treatment has been brought about by the emergence of a novel approach utilizing oncolytic viruses in cancer immunotherapy. Oncolytic viruses are viruses that have been exploited genetically to assault malignant cells and activate a robust immune response. Several techniques have been developed to endow viruses with an oncolytic activity through genetic engineering. For instance, redirection capsid modification, stimulation of anti-neoplastic immune response, and genetically arming viruses with cytokines such as IL-12. Oncolytic viral clinical outcomes are sought after, particularly in more advanced cancers. The effectiveness and safety profile of the oncolytic virus in clinical studies with or without the combination of standard treatment (chemotherapy, radiotherapy, or primary excision) has been assessed using response evaluation criteria in solid tumors (RECIST). This review will comprehensively outline the most recent clinical applications and provide the results from various phases of clinical trials in a variety of cancers in the latest published literature.
Image Source: Zheng et al., 2019 [6]. Use Permitted For non-commercial purposes: Creative Commons Attribution – NonCommercial – NoDerivs (CC BY-NC-ND 4.0)
Virotherapy has been shown to have a noticeable impact on malignant cells through direct toxic replicating effects and immunostimulatory activity at the molecular level, which leads to the induction of complex apoptotic pathways. Several viruses, including adenovirus, HSV, measles virus, and VV, have been manipulated and genetically engineered to possess an oncolytic effect. Depending on the desired site and stage of malignancy, OVs can be administered via a variety of routes. For instance, the IT route is used in melanoma, the IV route in disseminated cancer, and the intrathecal route in CNS tumors. Nonetheless, the tumor microenvironment and antiviral immunity might be potential pitfalls that restrict and minimize OV delivery and therapeutic effects.
Multiple clinical applications of OVs in combination with other standard or complementary treatment modalities have demonstrated outstanding objective clinical outcomes according to RECIST criteria in advanced late-stage cancers with tumor regression, prolongation of OS compared to standard treatment alone, and a manageable safety profile. Among different types of cancer, melanoma, brain tumors, CRC, and prostate cancer are examples of successful utilization of OVs in a clinical setting. Currently, there are a marked number of clinical trials evaluating the efficacy and safety of anti-neoplastic viruses in various types of solid tumors. We hope future successes will tackle the current challenges concerning the therapeutic limitations of virotherapy.
The authors have declared that no competing interests exist.
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