The Battle Continues: Facing the Obstacles of Oncolytic Virotherapy Development

Immunotherapy has shown to be a potential treatment for a variety of cancers in recent decades. Oncolytic viruses (OVs) could well be designed to proliferate and lyse tumor tissues selectively while sparing normal non-neoplastic host cells and boosting antitumor immunity, providing a unique immunotherapeutic approach for cancer treatment.

Given their possibility, OVs still have a number of limitations that must be addressed in order to enhance their virotherapy efficacy. These include factors such as viral tropism, delivery platforms, viral distribution, dosing strategies, and antiviral immunity.

l Choose An Optimal OV

A wide range of different viral species has been investigated as prospective cancer therapeutic agents, including oncolytic adenoviruses, type 1 herpes simplex virus (HSV), polioviruses, measles virus (MV), Newcastle disease virus (NDV), reoviruses, vesicular stomatitis virus (VSV), and Zika virus. Given different kinds of tumors of diverse histologic origins, although some viruses exhibit a native tropism for tumors, they cannot readily match given OVs specifically with a certain kind of malignancy.

The envelope and size of the OV, tumor tropism, potential pathogenicity, immunogenicity, druggability, and viral stability are important factors to be considered in virus selection.

l Retarget OVs

To enhance an OV’s tropism and to reduce its adverse effects, different technologies varying from genetics to chemistry have been used to retarget OVs, and some are being evaluated in clinical trials. Retargeting approaches can be divided into three main categories: capsid development, genome engineering, and chemical modifications.

However, there is still insufficient knowledge on each OV’s surface binding, internalization, and gene expression properties.

l Construct Efficient OV Delivery Platforms

Although the greatest effect of OVs consists of their selective infection and replication in cancer cells, the ability to deliver OV particles efficiently to tumors still constitutes a huge hindrance. The rapid growth of tumors, impaired blood supply, abnormal lymphatic networks, vascular hyperpermeability inside tumors, the dense extracellular matrix (ECM) of solid tumors, and the antiviral functions of the host’s immune system all reduce the efficacy and delivery of OVs.

l Maintain the Balance Between Antiviral Immunity and Antitumor Immunity

Another challenge is the presence of innate and adaptive antiviral immune responses evoked by OVs, which can lead to the quick clearance of OVs and limit their antitumor efficacy. Multiple strategies have been envisaged to suppress antiviral immunity, including the use of immunomodulators, genetic manipulation, antioxidant sulforaphane, cytokines, etc.

However, some investigators advocate that OV-induced antiviral immune responses are beneficial to antitumor immunity because they can overturn tumor-associated immunosuppression, and lead to virus-induced immunogenic cell death, thereby activating antitumor immunity. Thus, it’s necessary to develop strategies to manage antiviral immunity, to enhance antitumor immune activity, and to maintain the balance between them.

Oncolytic virotherapy is a promising cancer immunotherapy. With the advancement of modern genetic engineering techniques, a growing number of researchers are discovering strategies to improve the construction of OVs, reduce clinical toxicity, build novel delivery platforms, and boost OV efficacy, all with the goal of achieving the greatest therapeutic benefit.

With years of research in immunotherapy, Creative Biolabs provides customized and reliable oncolytic virus therapy development services covering all aspects from oncolytic virus engineering, cell biology, to animal testing with a special emphasis on virus engineering and in vitro and in vivo validation. Creative Biolabs is dedicated to assisting global scientists to accelerate their researches and explore a better strategy for oncolytic virotherapy.

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