Oncolytic virus therapies have shown promising efficacy in solid tumors in several clinical trials. Comparing to non-replicating gene virus therapy, such as retrovirus, replicating oncolytic virus can be shed from treatment in patients and transmitted into the environment or healthy people. However, oncolytic virus itself may also induce certain toxicity in vivo. For example, HSV may infect neuron cells and keep a latent status. Vaccinia virus may infect the human reproductive system. Though most of oncolytic viruses have been attenuated by mutations or deletions, the modified viruses may revert to wild type virus and infect normal host tissues. The toxicity of oncolytic virus mainly comes from the virus and/or the expressed transgene. Oncolytic virus has some off-target effects which may induce toxicity. Creative Biolabs has developed various assays to analyze the toxicity of oncolytic virus and the expressed transgene. Our toxicology studies of oncolytic virus include.
Shedding study will provide information about the likelihood of transmission of oncolytic virus to untreated individuals. The design of the virus shedding study depends on the virus replication competence, immunogenicity, persistence, latency, tropism, and the route of administration. Non-clinical shedding studies can be useful in preparing for clinical studies and evaluating detection methods.
Clinical observations include but are not limited to body weight, appetite, and morbidity/mortality.
Clinical pathology includes but is not limit to hematology, coagulation, clinical chemistry, and urinalysis.
Gross organ pathology includes weight of brain, liver, kidney, lung, heart, spleen, testes, and ovaries.
Histopathology of the brain, liver, kidney, lung, heart, spleen, testes, ovaries, bone marrow, and quadriceps muscle.
A transgene study is designed according to the property of transgene, such as antibody, ligand-receptor binding, or distribution. For example, the transgene is an antibody and all toxicity related to antibody development should be performed.
Oncolytic viruses are usually adapted or mutated to increase the tumor cell infection specificity. However, in some circumstances, the mutated oncolytic virus can still infect normal cells, such as hematopoietic cells, neurons, muscles, and the reproductive system. Specific assays need to be developed to analyze the toxicity of different oncolytic virus.
Off-target toxicity can also come from the transgene that is engineered into oncolytic virus, such as antibody, growth factors, and cytokines. The toxicity generated from these transgene also has to be evaluated.
According to FDA guideline, present regulations require an integrated summary of the toxicologic effects of the pharmaceuticals in animals and in vitro. To support the safety of the proposed clinical investigation of oncolytic virus, specialists in Creative Biolabs will provide a full set of toxicology study in which the nature of virus species, engineered elements, animal model establishment, targeted disease and administration route are taken into consideration.
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