Immune response gene therapy products

One of the major concerns in the use of Ad vectors for gene therapy purposes is the induction of an innate immune response. Administration of an Ad vector causes inflammation of the infected tissue, especially in the liver (110, 113-115). The induction of chemokine production at the infected site attracts neutrophils, leading to necrosis and apoptosis in the liver. The development of gutless Ad vectors markedly reduce inflammatory responses and cellular infiltration (116). However, inflammation induced by the viral capsid proteins itself cannot be prevented (110). 

If the gene therapy causes the production of a protein that was previously absent in the body, then an immune response to the novel protein is likely. Resistance to gene therapy can result from immunization against either the construct or the vector. The former is analogous to the patients who used to become resistant to xenobiotic insulins (see above), and is also seen in the case of human factor VIII in some patients with hemophilia. Escalating doses may be needed to maintain efficacy, or efficacy may be eventually lost. On the other hand, viral vectors are liable to replicate and also to elicit immune responses, just as for any vaccination, creating many of the same problems. 

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