Oncolytic virus immunotherapy has shown promising anti-tumor effects in several clinical trials. However, immunogenicity, measured by anti-drug antibodies (ADA), is one of the most prominent problems when developing oncolytic viral drugs. Immunogenicity of oncolytic viral therapy includes innate and adaptive immune response to the oncolytic virus backbone and the transgene. Assays for immunogenicity analysis include antibody production against the oncolytic virus vector and transgene, neutralization antibody production against oncolytic virus, complement-mediated anti-oncolytic virus activity. Assays for oncolytic virus immunogenicity tests include:
Innate immune response test
During oncolytic viral therapy, the host immune system will generate an immune response to clear the virus infection. Innate immune response includes IFN and NK cells. Creative Biolabs has developed assays to evaluate the innate immune response against oncolytic viral infection.
Oncolytic virus can also be neutralized by the host complement system, which will directly affect the efficacy of oncolytic virus. Complement dependent killing tests will be used to test the immunogenicity of oncolytic virus.
Neutralization antibody production test
Adaptive immune response against oncolytic virus include antibody production during the treatment which can neutralize the virus and compromise the tumor cell killing efficacy. Neutralization antibody assay will be developed to test the antibody production during the treatment.
Host adaptive immune system not only generates antibodies against the virus, but also produces antibodies against the transgene engineered into oncolytic virus. Biacore assays can be developed to evaluate the ADA affect during the oncolytic virus treatment.
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