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 clinical use of reactogenic liposomes in cardiac patients, as a main manifestation of C activation in the body may be cardiopulmory distress. The adverse immune Janos Szebenia and Yechezkel (Chezy) Barenholzb a Nanomedicine Research and Education Center, Semmelweis University and Bay Zoltan Foundation for Applied Research, Budapest, and Faculty of Health Sciences, Miskolc University, Miskolc, Hungary b Laboratory of Membrane and liposome Research, Institute of Medical Research Israel Canada (IMRIC), The Hebrew University-Hadassah Medical School, Jerusalem, Israel Jszebeni2@gmail.com, yb@cc.huji.ac.il, chezyb@gmail.com Handbook of Harnessing Biomaterials in Nanomedicine: Preparation, Toxicity, and Applications Edited by Dan Peer Copyright © 2012 Pan Stanford Publishing Pte. Ltd. ISBN 978-981-4316-46-0 (Hardback), 978-981-4364-27-0 (eBook) www.panstanford.com 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.