Interferon alfa

Interferon alfa contains a mixture of several proteins, all with structural, serological, and functional properties typical for natural interferon alpha (IFN-α). The major subtypes identified are IFN-α1, IFN-α2, IFN-α8, IFN-α10, IFN-α14 and IFN-α21. Of these, IFN-α2 and IFN-α14 are glycosylated. The IFN-α content is expressed in International Units per milliliter, and the drug product is formulated in isotonic phosphate buffer solution at pH = 7.2, and supplemented with human albumin at 1.5 mg/ml. The albumin used is a medicinal product approved in several countries, and is indicated for subcutaneous injection therapy.

IFN-α8 enhances the proliferation of human B cells, as well as being able to activate NK cells. The subtypes α10 and α2, along with α8, are the most efficient and powerful NK cell activators. Subtypes α21 and α2 enhance the expression of IFN-gamma-inducible protein-10 (IP-10) in dendritic cells. Activated dendritic cells initiate immune responses and induce the expression of IP-10, a chemokine which promotes a Th1 inflammatory response.

IFN-α1 causes increased HLA-II expression, and can directly inhibit tumor cell growth in vitro. However, it is a poor activator of NK cells, has relatively little antiviral activity, does not induce B cell proliferation, and does not enhance HLA-I or tumor antigen expression. Despite its apparent inactivity, it is still used clinically in the treatment of metastatic renal cell carcinoma, with a reported lower toxicity than the recombinant IFN-α2. Overall, IFN-α has a general inflammatory action which skews the immune response towards a Th1 profile.

Subtype α2 increases the expression of HLA-I molecules, which correlates with IFN-α-mediated activation of memory CD8 cells and increased cytolytic action against virally infected cells and tumor cells (via cytotoxic CD8 cells).