Mechanisms of Action of Oncolytic Virus Destroying Tumor Cells
Oncolytic virus refers to viral strains that continuously replicate in tumor cells and lyse the cells to kill malignant cells. Recently, the focus in the OV therapy field has shifted from their direct oncolytic effect to their immune stimulatory effect.
Cancer immunotherapies focus on strengthening the recognition and elimination of cancer cells by the host immune system. Mounting clinical data now conclusively demonstrate the positive correlation between the presence of such antitumor immune responses and favorable patient outcomes for many cancers. Although originally discovered for their oncolytic activities, OVs are now being increasingly recognized for their anticancer immunotherapeutic qualities.
Creative Biolabs has summarized the mechanism of action of oncolytic virus and builds the best oncolytic virus service platform to assist with your research work.
Tumor Cell Lysis and the Induction of System Immune Response
- Upon infection with an oncolytic virus, the oncolytic virus repeats in tumor cells and causes oncolysis.
- The release of viral progeny propagates the infection with the adjacent uninfected oncolytic virus and depletion of immunosuppressive cell types such as cancer-associated fibroblasts (CAFs).
- Subsequently, dissolved cells release viral progeny and tumor associated antigens (TAAs) including neo-antigens, pathogen-associated molecular patterns (PAMPs) and danger-associated molecular pattern signals (DAMPs).
- The TAAs and neo-antigens are released and taken up by antigen presenting cells (APCs) such as dendritic cells, which participate in antigen processing and presentation, including increasing major histocompatibility complex (MHC) class I and MHC class II expression on APCs, thus increasing the expression of the MHC–peptide–TCR complex.
- The PAMPs consist of viral particles while DAMPs comprise host cell proteins, such as extracellular ATP, high-mobility group protein B1 (HMGB1), surface-exposed calreticulin and increased heat shock protein 70 (HSP70). Both of them can contribute to the maturation and function of dendritic cells and stimulate the immune system by triggering activating receptors such as Toll-like receptors (TLRs) expressed on surface of NK cells and dendritic cells.
- In the context of the resulting immune stimulatory environment, collectively, these events result in the generation of immune responses against virally infected tumor cells, as well as de novo immune responses against TAAs/neo-antigens displayed on uninfected tumor cells.
Figure 1 Mechanisms of action of oncolytic viruses destroying tumor cells
Anti-viral immune response enhances system immune response
Upon infection with an oncolytic virus, tumor cells immediately initiate an antiviral response that consists of endoplasmic reticulum (ER) and genotoxic stress, leading to the upregulation of reactive oxygen species (ROS) and the initiation of antiviral cytokine production. ROS and cytokines, specifically type I interferons (IFNs), are released from the infected cancer cells and stimulate immune cells (antigen presenting cells, CD8+ T cells, and natural killer (NK) cells), thus causing a harsh environment for tumor cells.
Although the mechanisms of action of oncolytic viruses are still incompletely understood, it appears that the therapeutic efficacy of oncolytic viruses is determined by a combination of direct tumor cell lysis and indirect activation of anti-tumor immune responses. Creative Biolabs has provided you with more detailed message about inherent and engineered oncolytic viruses. Based on the professional oncolytic virus engineering platform, Creative Biolabs has developed a series of engineered oncolytic viruses to enhance tumor lysis and immune response.