Oncolytic Virus Toxicology Study Service
Conducting toxicological research on oncolytic viruses is crucial as it comprehensively ensures safety for clinical use by assessing impacts on tissues, organs, and immune responses, guiding genetic engineering to optimize virus design and efficacy. Creative Biolabs has developed a series of rich and advanced detection methods for comprehensive and accurate analysis of the toxicity of oncolytic viruses and their expressed transgenes with its technology accumulation and innovative spirit.
Source of Oncolytic Virus Toxicity
Tab.1 The causes of the toxicity of oncolytic viruses.
| The characteristics of viruses | Genetically engineered virus strains may retain some potential pathogenicity. For instance, some AD can trigger immune responses causing fever, HSV shows neurotoxicity, and VV may be toxic to the reproductive system. |
| Viral load: Higher doses of oncolytic viral agents may increase the risk of normal tissue infection. When a large number of viral particles enter the bloodstream, they can impose a greater burden on the liver and kidneys. | |
| The impacts of gene editing | Insertional Mutations: During gene editing, inserted foreign genes may randomly integrate into the host cell genome. This can activate proto-oncogenes or silence tumor-suppressor genes, increasing tumorigenesis risk. |
| Gene Expression Dysregulation: The gene expression regulation of the edited virus may be altered, resulting in abnormal expression levels of certain virulence genes, which in turn exert toxic effects on host cells. | |
| Factors related to the immune response | Innate Immune Activation: Oncolytic viruses, upon infecting cells, activate the body's innate immune response, releasing numerous cytokines like TNF-α and IL-6. Excessive activation can trigger a cytokine storm, resulting in a systemic inflammatory response and multi-organ damage. |
| Adaptive immune response: In the process of adaptive immune response, immune cross-reactions may occur, leading to autoimmune damage. | |
| Lysis products of tumor cells | Upon tumor lysis, tumor-associated antigens, nucleic acid fragments, etc. are released. These trigger the body's immune response and irritate surrounding normal tissues, causing local inflammation and immune damage. |
Safety Evaluation in Preclinical Studies
- Monitoring of General Physiological Indicators
The general condition of the animals is monitored daily, including measurements of body temperature, and heart rate, as well as observations of weight change, mental state, mobility, and dietary alterations. Weight loss, lethargy, and reduced activity levels might be early indications of viral virulence.
- Liver and Kidney Function and Blood Glucose Monitoring
During the treatment period, the levels of blood urea nitrogen (BUN), creatinine (CRE), aspartate aminotransferase (AST), alanine aminotransferase (ALT), and glucose (GLU) are measured.
- Hematology and Coagulation Tests
Blood samples are systematically collected from individuals in both the experimental group and the control group. Key hematological parameters are monitored, including white blood cell (WBC) count, red blood cell (RBC) count, and hemoglobin (Hb) level. Additionally, multiple other indicators such as lymphocyte count, platelet count, neutrophil (NEU) count, prothrombin time (PT), activated partial thromboplastin time (APTT), and fibrinogen (Fib) level are assessed.
- Histopathology
After the experiment, the animals are humanely euthanized. The main organs and tissues, including the heart, liver, spleen, lung, kidney, and brain, are harvested for pathological sectioning and HE staining. This is to observe histomorphological alterations and determine the presence of pathological changes such as inflammation, necrosis, and apoptosis. Additionally, immunohistochemistry and other techniques could be employed to detect specific markers, thereby further analyzing the causes and mechanisms of tissue damage.
- Off-target effect detection
There are various methods for detecting the off-target toxicity of oncolytic viruses. The injury can be judged by histopathological examination and observation of the morphology of cells in tissues by HE staining. Blood biochemical indexes are detected, and the changes in liver and kidney function indexes indicate the affected organs. Immunohistochemistry and in situ hybridization can also be used to determine virus infection in normal tissues and the site and severity of off-target toxicity.