Recombinant Viral Vectors for Therapeutic Programming of Tumour Microenvironment: Advantages and Limitations

Abstract

Viral vectors have been widely investigated as tools for cancer immunotherapy. Although many preclinical studies demonstrate significant virus-mediated tumour inhibition in synergy with immune checkpoint molecules and other drugs, the clinical success of viral vector applications in cancer therapy currently is limited. A number of challenges have to be solved to translate promising vectors to clinics. One of the key elements of successful virus-based cancer immunotherapy is the understanding of the tumour immune state and the development of vectors to modify the immunosuppressive tumour microenvironment (TME). Tumour-associated immune cells, as the main component of TME, support tumour progression through multiple pathways inducing resistance to treatment and promoting cancer cell escape mechanisms. In this review, we consider DNA and RNA virus vectors delivering immunomodulatory genes (cytokines, chemokines, co-stimulatory molecules, antibodies, etc.) and discuss how these viruses break an immunosuppressive cell development and switch TME to an immune-responsive “hot” state. We highlight the advantages and limitations of virus vectors for targeted therapeutic programming of tumour immune cell populations and tumour stroma, and propose future steps to establish viral vectors as a standard, efficient, safe, and non-toxic cancer immunotherapy approach that can complement other promising treatment strategies, e.g., checkpoint inhibitors, CAR-T, and advanced chemotherapeutics.

An Overview of Adenovirus Vector-based Vaccines against SARS-CoV-2

“…In the context of clinical trials, a single administration of Ad26.COV2.S elicited rapid binding, neutralization antibody responses, and cellular immune responses in a phase I study in 25 healthy volunteers (Ricobaraza et al, 2020). Moreover, 1,045 healthy volunteers were vaccinated with a single dose of 1 × 10 10 or 5 × 10 10 Ad26.COV2.S particles in phase I/II study showed good safety and strong immune responses (Spunde et al, 2022).…”

“…Several human adenovirus serotypes were widely distributed and infected the majority of infants and young children in the early stages of their lives (Ricobaraza et al, 2020). According to several studies, 45% to 80% of persons had antibodies that neutralized AdHu5 viruses (Spunde et al, 2022). Depending on the location where they live, 5-15% of adults had virusneutralizing antibodies to AdHu 35.…”

“…The capacity of adenoviruses to bind to host cell receptors is known as tropism (Baron et al, 2018;Spunde et al, 2022). The distal knob domain of the fiber initially binds to the coxsackie adenovirus receptor (CAR), which is expressed on many cell types, including hepatocytes, the basolateral surface of epithelial cells, endothelial cells, myoblasts, and heart muscle cells.…”

Aptamers Enhance Oncolytic Viruses’ Antitumor Efficacy

“…They are considered the most adapted and clinically developed vectors. On the other hand, their use is limited in clinical practice due to the possibility of non-specific vector integration and insertional mutagenesis of any viral DNA vector [ 38 , 39 ]. The use of RNA viruses, despite their many attractive properties, is limited due to the complexity of genetic manipulations even with modern genetic technologies [ 40 ].…”

“…Often, a viral drug is administered intratumorally, but due to the need to treat metastases, it becomes necessary to administer it systemically. However, replication-competent viral vectors are best administered for local intratumoral administration in order to reduce toxicity, while replication-deficient vectors having proposed tumor affinity can be used for systemic delivery [ 39 , 45 ]. For example, the extracellular enveloped virus, one of the two antigenically and structurally distinct infectious virions produced by the vaccinia viruses, is naturally resistant to antibody neutralization and complementarity and, therefore, could be used for systemic delivery [ 46 ].…”