title: Targeting complement in therapy.
abstract: With increasing evidence that complement activation significantly contributes to the pathogenesis of a large number of inflammatory diseases, strategies that interfere with its deleterious action have become a major focus in pharmacological research. Endogenous soluble complement inhibitors (C1 inhibitor, recombinant soluble complement receptor 1, antibodies) blocking key proteins of the cascade reaction, neutralizing the action of the complement-derived anaphylatoxin C5a, or interfering with complement receptor 3 (CR3, CD18/11b)-mediated adhesion of inflammatory cells to the vascular endothelium have successfully been tested in various animal models over the past years. Promising results consequently led to clinical trials. Furthermore, incorporation of membrane-bound complement regulators (decay-accelerating factor (CD55), membrane co-factor protein (CD46), CD59) in transgenic animals has provided a major step forward in protecting xenografts from hyperacute rejection. At the same time, the poor contribution of complement to the antitumor response, which is caused by multiple resistance mechanisms that hamper the efficacy of antibody-based tumor therapy, is increasingly recognized and requires pharmacologic intervention. First attempts have now been made to interfere with the resistance mechanisms, thereby improving complement-mediated tumor cell destruction.
authors: Institute of Immunology, University of Heidelberg, Germany. k92@ix.urz.uni-heidelberg.de
authors: M
authors: M
authors: Kirschfink
mesh_terms: D000706:Anaphylatoxins / Q000037:antagonists & inhibitors / Q000276:immunology; D000799:Angioedema / Q000188:drug therapy; D000818:Animals; D030801:Animals, Genetically Modified; D000893:Anti-Inflammatory Agents / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D000912:Antibodies, Neoplasm / Q000627:therapeutic use; D001550:Benzamidines; D003167:Complement Activation / Q000187:drug effects*; D003174:Complement C1 Inactivator Proteins / Q000627:therapeutic use; D003169:Complement Inactivator Proteins / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D015938:Complement Membrane Attack Complex / Q000037:antagonists & inhibitors / Q000276:immunology; D003165:Complement System Proteins / Q000737:chemistry / Q000502:physiology*; D004285:Dogs; D015195:Drug Design; D004353:Drug Evaluation, Preclinical; D006084:Graft Rejection / Q000517:prevention & control; D006146:Guanidines / Q000627:therapeutic use; D006801:Humans; D007167:Immunotherapy; D007249:Inflammation / Q000276:immunology / Q000517:prevention & control; D008252:Macaca fascicularis; D051379:Mice; D009369:Neoplasms / Q000276:immunology / Q000628:therapy; D010195:Pancreatitis / Q000188:drug therapy; D011817:Rabbits; D051381:Rats; D011951:Receptors, Complement / Q000187:drug effects; D017463:Receptors, Complement 3b / Q000627:therapeutic use; D015427:Reperfusion Injury / Q000188:drug therapy; D013552:Swine; D014019:Tissue Donors; D014162:Transfection; D014183:Transplantation, Heterologous
chemical_list: D000706:Anaphylatoxins; D000893:Anti-Inflammatory Agents; D000912:Antibodies, Neoplasm; D001550:Benzamidines; D003174:Complement C1 Inactivator Proteins; D003169:Complement Inactivator Proteins; D015938:Complement Membrane Attack Complex; D006146:Guanidines; D011951:Receptors, Complement; D017463:Receptors, Complement 3b; D003165:Complement System Proteins; C032855:nafamostat