Immunogenicity of interferon-alpha2 in therapy: Structural and physiological aspects

Recombinant human interferon (rIFN)-alpha2 has been approved for therapeuti c application in a range of human oncological and viral diseases. However, some patients can develop strictly specific antibody response to rIFN-alpha 2, which may diminish its therapeutic potential. Such humoral response appe ars to be quite complex and obviously depends on multiple parameters. Our r eview is aimed primarily to factors associated with structural modification s of rIFN-alpha2 that we consider crucial for formation of therapy-induced antibodies. These factors are either related to inherent conformational dif ferences between three IFN-alpha2 subvariants or to immunogenically active contaminating derivatives resulting from production, purification and stora ge of this recombinant protein. In addition, the role of treatment regimen and physiological variables modulating the immune response to rIFN-alpha2 i n the challenged organism are mentioned.