Immunogenicity by Aggregation of Therapeutic Proteins from Ultraviolet Radiation Produced in the Human Body by Nanoparticles of the Aggregates Themselves

Abstract

Protein therapeutics is used in the treatment of diabetes and various forms of cancer. A major concern is that repeated administration to patients often leads to undesirable antidrug antibodies with a wide range of life threatening consequences that induce immunogenicity or an adverse response of the immune system. The antibodies are generally thought triggered by the tendency of monomer protein molecules to aggregate, although why aggregation occurs is not known. In protein deposition diseases such as Alzheimer and Parkinson, protein aggregates have stronger immunogenicity. Typically, the aggregates known to elicit immunogenicity are globular proteins having molecular weights from 6-100 kDa and diameters from 3-10 nm that are comparable to inanimate natural or manmade nanoparticles that have been linked to damage of deoxyribonucleic acid by the natural emission of low-level ultraviolet radiation induced by quantum electrodynamics. Similarity suggests the protein aggregates form as monomers cross-link under ultraviolet radiation produced by nanoparticles of the aggregates themselves. How immunogenicity may be reduced is discussed.