Oncolytic Virus and Strategies to Enhance Its Tumor-killing Efficacy

Oncolytic viruses (OVs) are a group of viruses that preferentially infect and kill tumor cells without harming healthy cells, and induce a strong immune response within the tumor, thereby altering the immunosuppressive microenvironment and activating immune cells to kill the tumor. This kind of virus includes genetically engineered or natural viruses.

With the advancement of genetic engineering technology and in-depth research on tumor immunotherapy in recent years, various improved strategies to enhance OVs have been proposed, and nowadays, oncolytic virus therapy has the advantages of high killing efficiency, good targeting, low side effects, multiple tumor killing pathways and low cost, which is a promising development direction in the field of tumor immunity.

At present, domestic and foreign research and development of OVs is in full swing, and the understanding of OVs is deepening as the virus modification project is improving and updating.

1.Armored OVs

Engineered virus is to insert exogenous genes into the viral sequence to enable them to express tumor antigen antibodies or immune activating cytokines, etc. This modification strategy, also commonly referred to as armored OVs, loads the virus itself with new "weapons" to achieve better killing effects.

The antibodies usually chosen for expression are usually more established tumor antigens, such as PD-1/L1 and CTLA-4. This is because of their proven clinical efficacy on the one hand, and safety considerations on the other.

GM-CSF is the commonly used immune activating cytokine. In addition to GM-CSF, other immunomodulatory factors such as immune-related cytokines (IL-2, interferon), chemokines (CCL5, CCL20, CCL21), and other factors that can induce anti-tumor immune responses (viral membrane proteins, HSP70) are also popular choices.

2.OV combination therapy

OVs can realign the immunosuppressive microenvironment of solid tumors, turning cold tumors into hot tumors. At the same time, there is growing clinical evidence that OVs can enhance the response of tumors to immunotherapy approaches such as immunomodulatory checkpoint inhibitors and CAR-T cells. Therefore, the combination of OVs and other immunotherapies to enhance tumor killing has become a popular research direction.

As early as 2017, a research scholar suggested that the overall remission rate of OVs in combination with PD-1 antibodies reached 61.9%, complete remission rate reached 33%, and objective response rate (ORR) of tumors was improved by more than 55% compared with monotherapy.

In addition to combining with immune checkpoint inhibitors such as PD-1, OVs are also being tested in combination with CAR-T cells as an oncology treatment strategy.

3.Routes of administration

Currently, OVs are generally administered by local/intra-tumoral injection due to the nature of the virus

In general, if OVs are administered intravenously, they are likely to interact with factors in the blood and lead to inactivation; in addition, natural immunoglobulin M (IgM) antibodies can bind to human oncolytc adenovirus, leading to capture of the virus by the immune system in liver macrophages, promoting infection of hepatocytes and causing hepatotoxicity. However, the accessibility can be greatly expanded if intravenous or other routes of administration can be achieved.

OVs are a hot trend in tumor immunization today, and although their applications are not yet widespread, they have demonstrated good anti-tumor effects in several clinical studies, covering melanoma, nasopharyngeal carcinoma, head and neck tumors, and many other areas. It is hoped that as new clinical study data continue to be unveiled, its indications will be further expanded and its efficacy will be better in the future, thus bringing new hope to tumor patients.

Candy Swift: Focus on the cutting edge biological information around the world.