The wonders of gene therapy using technologies to deliver or modify genes to treat inherited diseases, cancer, and other disorders is just becoming a reality. So far only a few such therapies have been approved. For example, Spark Therapeutics, Luxturna (voretigene neparvovec-rzyl) for an inherited form of blindness, and Zolgensma for spinal muscular atrophy are the only approved gene therapies in the USA for inherited genetic diseases. Many more of these life changing therapies are navigating clinical trials and some will be approved in the coming months and years. But many challenges confront gene therapy. The viral vectors used to deliver the gene therapy elicit an immune response or are met with an experienced immune system ready to stop the viral vectors before they can deliver the payload.
Gene therapies rely on adeno-associated virus (AAV), adeno virus, lentivirus, Herpes Virus, or another modified viral vector. In the case of AAV, approximately 70% of adults have antibodies and memory T cells that can bind and clear the vector. The viral capsid proteins are displayed by antigen presenting cells and rally an adaptive immune response.
Manufacturing high quality viral vectors requires specialized services. The gene therapy vectors should be assessed by immuno-assay, viral titer, infectious titer, host cell protein contaminants and stability. High quality gene therapies need to be well characterized and free of host proteins, degradation products, impurities or other manufacturing related liabilities that increase the risk of an immune response. BioTether Sciences team has experience working with viral vectors and assessing immunogenicity risk.
Antibodies to AAV and other viral vectors can be detected by pre-screening clinical trial subjects and monitoring them during therapy Pre-existing antibodies or newly formed antibodies can be measured using an ELISA. Screening patients for viral antibodies may be helpful to design an effective clinical trial and improve safety. Tracking immunogenicity of gene therapy vectors during clinical trials and correlating the antibody response to efficacy and safety is important for a successful, FDA compliant, and safe clinical trial.