Complement activation, immunogenicity, and immune suppression as potential side effects of liposomes

Some therapeutically relevant liposomes are recognized by the immune system as foreign, and the resulting innate or specific immune response can be adverse to the host. The innate response can involve the activation of the complement (C) system, which, via liberation of anaphylatoxins (C5a, C3a), underlies an acute hypersensitivity syndrome called C activation-related pseudoallergy (CARPA). CARPA represents a potential barrier to the clinicai use of reactogenic liposomes in cardiac patients, as a main manifestation of C activation in the body may be cardiopulmory distress. The adverse immune response to liposomes involving specific immunity is exemplified by PEGylated nanoliposome-induced transient IgM production, which causes accelerated blood clearance (ABC). Immunosuppression occurs mostly with anticancer and antifungal liposomes. This chapter updates the information on CARPA, accelerated blood clearance (ABC phenomenon), and immunosuppression; highlights their common and specific causes; and discusses their mechanisms.