Clinical Application of Oncolytic Viruses: A Systematic Review

Abstract

Leveraging the immune system to thwart cancer is not a novel strategy and has been explored via cancer vaccines and use of immunomodulators like interferons. However, it was not until the introduction of immune checkpoint inhibitors that we realized the true potential of immunotherapy in combating cancer. Oncolytic viruses are one such immunotherapeutic tool that is currently being explored in cancer therapeutics. We present the most comprehensive systematic review of all oncolytic viruses in Phase 1, 2, and 3 clinical trials published to date. We performed a systematic review of all published clinical trials indexed in PubMed that utilized oncolytic viruses. Trials were reviewed for type of oncolytic virus used, method of administration, study design, disease type, primary outcome, and relevant adverse effects. A total of 120 trials were found; 86 trials were available for our review. Included were 60 phase I trials, five phase I/II combination trials, 19 phase II trials, and two phase III clinical trials. Oncolytic viruses are feverously being evaluated in oncology with over 30 different types of oncolytic viruses being explored either as a single agent or in combination with other antitumor agents. To date, only one oncolytic virus therapy has received an FDA approval but advances in bioengineering techniques and our understanding of immunomodulation to heighten oncolytic virus replication and improve tumor kill raises optimism for its future drug development.

Combinatorial Approaches for Cancer Treatment Using Oncolytic Viruses: Projecting the Perspectives through Clinical Trials Outcomes

“…Factors that impair viral proliferation and boost the rate of viral clearance in healthy tissue (IFN type I response genes, tumor suppressor proteins, etc.) are dysfunctional in tumor cells, enabling preferential replication of OVs [ 17 , 18 , 19 ]. Although some viruses exhibit inherent tropism for tumor cells, genetic engineering also helps to precisely tune up the virus life cycle to become the most potent cancer killer [ 20 , 21 , 22 , 23 ].…”

“…By May 2021, more than 200 clinical trials of diverse combinations of OVs and immunotherapies were found and many others are coming out on the regular basis. Oncolytic virus application is discussed in several immaculate reviews highlighting the results of completed clinical trials [ 18 , 19 ]. In this review, we will discuss combinations of oncolytic viruses and other cancer therapies currently studied in clinical trials with specific emphasis on their efficacy.…”

Design and Engineering of Deimmunized Vaccinia Viral Vectors

“…Various oncolytic viruses have been utilized to employ their tumor-specific killing activities by both direct (e.g., cell lysis due to viral replication and immune-mediated cytotoxicity) and indirect mechanisms (e.g., stimulation of the bystander cell killing, induction of cytotoxicity, etc.) [ 1 , 2 , 3 , 4 , 5 ]. Oncolytic vaccinia virus (VV) is an appealing addition to the current treatment options, demonstrating efficacy and safety in animal models and in early clinical studies [ 6 , 7 , 8 , 9 ].…”

Herpes Simplex Virus Oncolytic Immunovirotherapy: The Blossoming Branch of Multimodal Therapy

“…Big advances have been made in the development of HSV-based oncolytic viruses and the related therapeutic strategies, making HSV a forerunner in the field. Many other oncolytic viruses belonging to different virus families (adenovirus, measles virus, reovirus, vaccinia virus, parvovirus) are already at the clinical trial stage, and accompany oHSVs in their undertaking towards innovative, effective and personalized antitumor strategies [181,182]. The mentioned different virus families have diversified properties, but share similar challenges, notably their intricate relationship with the immune system of the host [162,170,183].…”