Adverse Immune Effects of Nanomedicines and Biologicals

J. Szebeni
Semmelweis University, HU

Keywords: immune reactivity, complement, CARPA, immunogenicity, immune suppression

Summary:

Induction of abnormal immune responses represents a major problem for many existing and prospective nanomedicines and biologicals. Possible manifestations include 1) immune suppression, 2) hypersensitivity reactions (HSRs), 3) immunogenicity and 4) cytokine storm. Immune suppression typically occurs because of lymphocyte or macrophage toxicity, often as a consequence of RES accumulation of cytotoxic nanodrugs. Hypersensitivity reactions are, in the majority of cases, non-IgE-mediated and may arise as a consequence of activation of the complement (C) system. C activation-related pseudoallergy (CARPA) can be severe or even lethal, as the symptoms include major cardiopulmonary and circulatory distress. Immunogenicity, i.e. formation of antibodies against nanomedicines and biologicals, can modulate their pharmacokinetics, and, hence, compromise their efficacy and safety. Finally, cytokine storm, another extremely severe immune toxicity phenomenon, is the result of inadvertent overstimulation of regulatory T cells. In addition to discussing the best-known examples of these adverse immune effects, their mechanisms and predictive in vitro and in vivo tests, the presentation will outline the current approaches for the prevention and treatment of immune toxic effects. There will be special focus on the prevention of liposome (Doxil)-induced CARPA by way of desensitization with empty (placebo) liposomes (Doxebo).