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Over the past few decades, immunotherapy has emerged as an effective therapeutic option against multiple malignancies. Oncolytic viruses (OVs) can be engineered to selectively replicate in and lyse tumor tissues while sparing the normal non-neoplastic host cells and simultaneously restoring antitumor immunity, which offers a novel immunotherapeutic approach for the treatment of tumors.

Despite the potential of OVs, there are still many limitations that should be tackled to improve their efficacy in virotherapy. These include factors such as viral tropism, delivery platforms, viral distribution, dosing strategies, antiviral immunity, etc.

Choosing the 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.

Retargeting 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.

Constructing 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.

Maintaining 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 immunotherapy for malignancies. With the development of modern genetic engineering techniques, increasing numbers of researchers are discovering strategies to optimize the construction of OVs, to reduce their clinical toxicity, to construct efficient OV delivery platforms, and to increase the efficacy of OVs, with the aim of achieving the greatest therapeutic benefit.

The latest research also found that oncolytic virotherapy can be combined with other treatments such as immunosuppressive drugs, which shows a better outcome in tumor treatment. It’s believed that such combination therapy could be new hope for patients suffering from cancer.

Just like a stuffed suitcase unloaded from the belly of a cargo plane, molecular backpacks called exosomes are constantly produced from the cells of the body. Each backpack is filled with a variety of materials that might be opened by another cell. By sending these biological packages, cells communicate with each other through shared proteins and genetic materials.

Due to the unique function of exosomes as intercellular messengers, the ability to change the biological activity of recipient cells, and their therapeutic potential in disease diagnosis and targeted drug delivery, the relationship between exosomes and different kinds of diseases has received widespread attention in recent years. One of them is diabetes, as exosomes are found to play an important role in insulin sensitivity, glucose homeostasis, and vascular endothelial function.

Diabetes is a common metabolic disorder, which is characterized by dysfunction of insulin secretion by pancreatic β cells and varying degrees of insulin lack. Organs such as the pancreas, liver, muscle, or fat are all involved, and communication between these organs is a key to maintain glucose homeostasis.

Type 1 diabetes mellitus (T1DM) and Type 1 diabetes mellitus (T2DM) have different pathogenesis. T1DM is due to the gradual loss of insulin-producing cells, resulting in low or none secretion of insulin. T2DM is due to the body’s production of insulin resistance. Although the pathogenesis of T1DM and T2DM is different, their pathogenic factors, pathophysiology, disease progression and complications are related.

Exosomes and T1DM

Exosomescontain powerful immunostimulatory substances. Exosomes released by insulinomas can stimulate the autoimmune response of non-obese diabetic (NOD) mice. This research shows that exosomes are the autoantigen carriers of NOD mice and have strong immune activity, which may be the trigger of autoimmunity in NOD mice.

Islet cell transplantation is an effective method for the treatment of autoimmune T1DM. Explants that are specifically released into the blood circulation by islet transplantation are of potential diagnostic value in distinguishing recurrent autoimmune and immune rejection from islet β-cell injury. Biological markers that can be used in the diagnosis of islet transplantation. Exosomes isolated from MSCs have immunomodulatory effects and can improve islet function by increasing the number of regulatory T cells and their anti-inflammatory products IL-4 and IL-10, so they can be used to treat T1DM.

Exosomes and T2DM

Exosomes carry important biological information about the pathogenesis of T2DM. The exosomes and the miRNAs they carry pass from the adipose tissue through the blood and penetrate into the skeletal muscle and liver. The reaction induced during this tissue migration may directly lead to the intercellular communication of T2DM and metabolism-related disorders. The miRNA contained in the exosomes secreted by islet cells regulates β-cell function in a paracrine manner, and this situation is significantly different between normal and T2DM patients.

Due to the complexity of clinical manifestations of different types of diabetes, sometimes it cannot be identified by current laboratory methods. Therefore, it is urgent to find a marker that can reflect pathophysiological characteristics or disease progression in real time. At the same time, such markers should be cheap and easy to obtain.

“Studies have shown that exosome marker can be used for early diagnosis and staging of diabetes, and exosome itself is also a target for the treatment of diabetes.” Said a scientist of Creative Biolabs, ‘more importantly, it can help to monitor the response of patients with diabetes to treatment and thus provide personalized treatment.”

With years of exploration in exosome services, Creative Biolabs has been committed to bringing together highly skilled experts applicable to exosome services to support exosome applications in diagnostics and novel therapeutics development, including sampling, analysis, manufacturing and exosome-based application services.