Archivum Immunologiae et Therapiae Experimentalis

, Volume 59, Issue 6, pp 407–419 | Cite as

Complement in Cancer and Cancer Immunotherapy



Recently, there has been an increase of interest in the use of biological or immune-based therapies for patients with malignancies. This has been informed by the deeper understanding of the crosstalk between the host immune system and malignant tumours, as well as the potential advantages of immunotherapy—high specificity and less toxicity compared to standard approaches. The particular emphasis of this article is on the role of the complement system in tumour growth and antibody-based cancer immunotherapy. The functional consequences from overexpression of complement regulators by tumours and the development of strategies for overcoming this are discussed in detail. This review discusses these issues with a view to inspiring the development of new agents that could be useful for the treatment of cancer.


Immunotherapy Cancer Complement Complement regulators Complement-dependent cytotoxicity (CDC) Antibody-dependent cell-mediated cytotoxicity (ADCC) 


  1. Ajona D, Hsu Y, Corrales L et al (2007) Down-regulation of human complement factor H sensitizes non-small cell lung cancer cells to complement attack and reduces in vivo tumor growth. J Immunol 178:5991–5998PubMedGoogle Scholar
  2. Aksamit R, Falk W, Leonard E (1981) Chemotaxis by mouse macrophage cell lines. J Immunol 126:2194–2199PubMedGoogle Scholar
  3. Astier A, Trescol-Biémont M, Azocar O et al (2000) Cutting edge: CD46, a new costimulatory molecule for T cells, that induces p120CBL and LAT phosphorylation. J Immunol 164:6091–6095PubMedGoogle Scholar
  4. Bjørge L, Matre R (1995) Down-regulation of CD59 (protectin) expression on human colorectal adenocarcinoma cell lines by levamisole. Scand J Immunol 42:512–516PubMedGoogle Scholar
  5. Bjørge L, Jensen TS, Ulvestad E et al (1995) The influence of tumour necrosis factor-alpha, interleukin-1 beta and interferon-gamma on the expression and function of the complement regulatory protein CD59 on the human colonic adenocarcinoma cell line HT29. Scand J Immunol 41:350–356PubMedGoogle Scholar
  6. Bjørge L, Hakulinen J, Vintermyr OK et al (2005) Ascitic complement system in ovarian cancer. Br J Cancer 92:895–905PubMedGoogle Scholar
  7. Blok V, Daha M, Tijsma O et al (1998) A bispecific monoclonal antibody directed against both the membrane-bound complement regulator CD55 and the renal tumor-associated antigen G250 enhances C3 deposition and tumor cell lysis by complement. J Immunol 160:3437–3443PubMedGoogle Scholar
  8. Blok VT, Gelderman K, Tijsma OH et al (2003) Cytokines affect resistance of human renal tumour cells to complement-mediated injury. Scand J Immunol 57:591–599PubMedGoogle Scholar
  9. Blom A, Villoutreix B, Dahlbäck B (2004a) Complement inhibitor C4b-binding protein-friend or foe in the innate immune system? Mol Immunol 40:1333–1346PubMedGoogle Scholar
  10. Blom A, Villoutreix B, Dahlbäck B (2004b) Functions of human complement inhibitor C4b-binding protein in relation to its structure. Arch Immunol Ther Exp 52:83–95Google Scholar
  11. Bodian D, Davis S, Morgan B et al (1997) Mutational analysis of the active site and antibody epitopes of the complement-inhibitory glycoprotein, CD59. J Exp Med 185:507–516PubMedGoogle Scholar
  12. Brasoveanu L, Altomonte M, Fonsatti E et al (1996) Levels of cell membrane CD59 regulate the extent of complement-mediated lysis of human melanoma cells. Lab Invest 74:33–42PubMedGoogle Scholar
  13. Brennan P, Donev R, Hewamana S (2008) Targeting transcription factors for therapeutic benefit. Mol Biosyst 4:909–919PubMedGoogle Scholar
  14. Bubeck D, Roversi P, Donev R et al (2011) Structure of human complement C8, a precursor to membrane attack. J Mol Biol 405:325–330PubMedGoogle Scholar
  15. Catterall C, Lyons A, Sim R et al (1987) Characterization of primary amino acid sequence of human complement control protein factor I from an analysis of cDNA clones. Biochem J 242:849–856PubMedGoogle Scholar
  16. Chen S, Caragine T, Cheung N et al (2000) CD59 expressed on a tumor cell surface modulates decay-accelerating factor expression and enhances tumor growth in a rat model of human neuroblastoma. Cancer Res 60:3013–3018PubMedGoogle Scholar
  17. Cherukuri A, Cheng PC, Pierce SK (2001) The role of the CD19/CD21 complex in B cell processing and presentation of complement-tagged antigens. J Immunol 167:163–172PubMedGoogle Scholar
  18. Cicardi M, Zingale L, Zanichelli A et al (2005) C1 inhibitor: molecular and clinical aspects. Springer Semin Immunopathol 27:286–298PubMedGoogle Scholar
  19. Coburn B, Li Y, Owen D et al (2005) Salmonella enterica serovar Typhimurium pathogenicity island 2 is necessary for complete virulence in a mouse model of infectious enterocolitis. Infect Immun 73:3219–3227PubMedGoogle Scholar
  20. Cooper N (1969) Immune adherence by the fourth component of complement. Science 165:396–398PubMedGoogle Scholar
  21. Cragg M, Glennie M (2004) Antibody specificity controls in vivo effector mechanisms of anti-CD20 reagents. Blood 103:2738–2743PubMedGoogle Scholar
  22. Davis AE 3rd, Mejia P, Lu F (2008) Biological activities of C1 inhibitor. Mol Immunol 45:4057–4063PubMedGoogle Scholar
  23. Di Gaetano N, Cittera E et al (2003) Complement activation determines the therapeutic activity of rituximab in vivo. J Immunol 171:1581–1587PubMedGoogle Scholar
  24. Donev RM, Gray LC, Sivasankar B et al (2008) Modulation of CD59 expression by restrictive silencer factor-derived peptides in cancer immunotherapy for neuroblastoma. Cancer Res 68:5979–5987PubMedGoogle Scholar
  25. Donin N, Jurianz K, Ziporen L et al (2003) Complement resistance of human carcinoma cells depends on membrane regulatory proteins, protein kinases and sialic acid. Clin Exp Immunol 131:254–263PubMedGoogle Scholar
  26. Ehrengruber MU, Geiser T, Deranleau DA (1994) Activation of human neutrophils by C3a and C5A. Comparison of the effects on shape changes, chemotaxis, secretion, and respiratory burst. FEBS Lett 346:181–184PubMedGoogle Scholar
  27. Fearon DT, Carroll MC (2000) Regulation of B lymphocyte responses to foreign and self-antigens by the CD19/CD21 complex. Annu Rev Immunol 18:393–422PubMedGoogle Scholar
  28. Fischer WH, Hugli TE (1997) Regulation of B cell functions by C3a and C3a(desArg): suppression of TNF-alpha, IL-6, and the polyclonal immune response. J Immunol 159:4279–4286PubMedGoogle Scholar
  29. Fishelson Z, Donin N, Zell S et al (2003) Obstacles to cancer immunotherapy: expression of membrane complement regulatory proteins (mCRPs) in tumors. Mol Immunol 40:109–123PubMedGoogle Scholar
  30. Flieger D, Renoth S, Beier I et al (2000) Mechanism of cytotoxicity induced by chimeric mouse human monoclonal antibody IDEC-C2B8 in CD20-expressing lymphoma cell lines. Cell Immunol 204:55–63PubMedGoogle Scholar
  31. Fukuoka Y, Hugli T (1988) Demonstration of a specific C3a receptor on guinea pig platelets. J Immunol 140:3496–3501PubMedGoogle Scholar
  32. Gancz D, Fishelson Z (2009) Cancer resistance to complement-dependent cytotoxicity (CDC): problem-oriented research and development. Mol Immunol 46:2794–2800PubMedGoogle Scholar
  33. Geis N, Zell S, Rutz R et al (2010) Inhibition of membrane complement inhibitor expression (CD46, CD55, CD59) by siRNA sensitizes tumor cells to complement attack in vitro. Curr Cancer Drug Targets 10:922–931PubMedGoogle Scholar
  34. Gelderman KA, Blok VT, Fleuren GJ et al (2002a) The inhibitory effect of CD46, CD55, and CD59 on complement activation after immunotherapeutic treatment of cervical carcinoma cells with monoclonal antibodies or bispecific monoclonal antibodies. Lab Invest 82:483–493PubMedGoogle Scholar
  35. Gelderman KA, Kuppen PJ, Bruin W et al (2002b) Enhancement of the complement activating capacity of 17–1A mAb to overcome the effect of membrane-bound complement regulatory proteins on colorectal carcinoma. Eur J Immunol 32:128–135PubMedGoogle Scholar
  36. Gelderman KA, Tomlinson S, Ross GD et al (2004) Complement function in mAb-mediated cancer immunotherapy. Trends Immunol 25:158–164PubMedGoogle Scholar
  37. Gelderman KA, Lam S, Sier CF et al (2006) Cross-linking tumor cells with effector cells via CD55 with a bispecific mAb induces beta-glucan-dependent CR3-dependent cellular cytotoxicity. Eur J Immunol 36:977–984PubMedGoogle Scholar
  38. Golay J, Zaffaroni L, Vaccari T et al (2000) Biologic response of B lymphoma cells to anti-CD20 monoclonal antibody rituximab in vitro: CD55 and CD59 regulate complement-mediated cell lysis. Blood 95:3900–3908PubMedGoogle Scholar
  39. Gorter A, Meri S (1999) Immune evasion of tumor cells using membrane-bound complement regulatory proteins. Immunol Today 20:576–582PubMedGoogle Scholar
  40. Guo RF, Ward PA (2005) Role of C5a in inflammatory responses. Annu Rev Immunol 23:821–852PubMedGoogle Scholar
  41. Hakulinen J, Meri S (1994) Expression and function of the complement membrane attack complex inhibitor protectin (CD59) on human breast cancer cells. Lab Invest 71:820–827PubMedGoogle Scholar
  42. Halperin JA, Taratuska A, Nicholson-Weller A (1993) Terminal complement complex C5b-9 stimulates mitogenesis in 3T3 cells. J Clin Invest 91:1974–1978PubMedGoogle Scholar
  43. Harjunpää A, Junnikkala S, Meri S (2000) Rituximab (anti-CD20) therapy of B-cell lymphomas: direct complement killing is superior to cellular effector mechanisms. Scand J Immunol 51:634–641PubMedGoogle Scholar
  44. Harris CL, Kan KS, Stevenson GT et al (1997) Tumour cell killing using chemically engineered antibody constructs specific for tumour cells and the complement inhibitor CD59. Clin Exp Immunol 107:364–371PubMedGoogle Scholar
  45. Hartmann K, Henz BM, Krüger-Krasagakes S et al (1997) C3a and C5a stimulate chemotaxis of human mast cells. Blood 89:2863–2870PubMedGoogle Scholar
  46. Heeger PS, Lalli PN, Lin F et al (2005) Decay-accelerating factor modulates induction of T cell immunity. J Exp Med 201:1523–1530PubMedGoogle Scholar
  47. Heinen S, Hartmann A, Lauer N et al (2009) Factor H-related protein 1 (CFHR-1) inhibits complement C5 convertase activity and terminal complex formation. Blood 114:2439–2447PubMedGoogle Scholar
  48. Hofman P, Hsi B, Manie S et al (1994) High expression of the antigen recognized by the monoclonal antibody GB24 on human breast carcinomas: a preventive mechanism of malignant tumor cells against complement attack? Breast Cancer Res Treat 32:213–219PubMedGoogle Scholar
  49. Idusogie EE, Wong PY, Presta LG et al (2001) Engineered antibodies with increased activity to recruit complement. J Immunol 166:2571–2575PubMedGoogle Scholar
  50. Imai M, Ohta R, Varela JC et al (2007) Enhancement of antibody-dependent mechanisms of tumor cell lysis by a targeted activator of complement. Cancer Res 67:9535–9541PubMedGoogle Scholar
  51. Jokiranta TS, Zipfel PF, Hakulinen J et al (1996) Analysis of the recognition mechanism of the alternative pathway of complement by monoclonal anti-factor H antibodies: evidence for multiple interactions between H and surface bound C3b. FEBS Lett 393:297–302PubMedGoogle Scholar
  52. Juhl H, Petrella EC, Cheung NK et al (1990) Complement killing of human neuroblastoma cells: a cytotoxic monoclonal antibody and its F(ab′)2-cobra venom factor conjugate are equally cytotoxic. Mol Immunol 27:957–964PubMedGoogle Scholar
  53. Juhl H, Sievers M, Baltzer K et al (1995) A monoclonal antibody-cobra venom factor conjugate increases the tumor-specific uptake of a 99mTc-labeled anti-carcinoembryonic antigen antibody by a two-step approach. Cancer Res 55(23 suppl):5749s–5755sPubMedGoogle Scholar
  54. Juhl H, Helmig F, Baltzer K et al (1997a) Frequent expression of complement resistance factors CD46, CD55, and CD59 on gastrointestinal cancer cells limits the therapeutic potential of monoclonal antibody 17-1A. J Surg Oncol 64:222–230PubMedGoogle Scholar
  55. Juhl H, Petrella EC, Cheung NK et al (1997b) Additive cytotoxicity of different monoclonal antibody-cobra venom factor conjugates for human neuroblastoma cells. Immunobiology 197:444–459PubMedGoogle Scholar
  56. Junnikkala S, Hakulinen J, Meri S (1994) Targeted neutralization of the complement membrane attack complex inhibitor CD59 on the surface of human melanoma cells. Eur J Immunol 24:611–615PubMedGoogle Scholar
  57. Junnikkala S, Jokiranta TS, Friese MA et al (2000) Exceptional resistance of human H2 glioblastoma cells to complement-mediated killing by expression and utilization of factor H and factor H-like protein 1. J Immunol 164:6075–6081PubMedGoogle Scholar
  58. Kemper C, Chan AC, Green JM et al (2003) Activation of human CD4+ cells with CD3 and CD46 induces a T-regulatory cell 1 phenotype. Nature 421:388–392PubMedGoogle Scholar
  59. Kemper C, Atkinson JP, Hourcade DE (2010) Properdin: emerging roles of a pattern-recognition molecule. Annu Rev Immunol 28:131–155PubMedGoogle Scholar
  60. Kennedy AD, Solga MD, Schuman TA et al (2003) An anti-C3b(i) mAb enhances complement activation, C3b(i) deposition, and killing of CD20+ cells by rituximab. Blood 101:1071–1079PubMedGoogle Scholar
  61. Kilgore KS, Schmid E, Shanley TP et al (1997) Sublytic concentrations of the membrane attack complex of complement induce endothelial interleukin-8 and monocyte chemoattractant protein-1 through nuclear factor-kappa B activation. Am J Pathol 150:2019–2031PubMedGoogle Scholar
  62. Kishore U, Reid KB (2000) C1q: structure, function, and receptors. Immunopharmacology 49:159–170PubMedGoogle Scholar
  63. Klos A, Tenner AJ, Johswich KO et al (2009) The role of the anaphylatoxins in health and disease. Mol Immunol 46:2753–2766PubMedGoogle Scholar
  64. Kraus S, Fishelson Z (2000) Cell desensitization by sublytic C5b-9 complexes and calcium ionophores depends on activation of protein kinase C. Eur J Immunol 30:1272–1280PubMedGoogle Scholar
  65. Kraus S, Seger R, Fishelson Z (2001) Involvement of the ERK mitogen-activated protein kinase in cell resistance to complement-mediated lysis. Clin Exp Immunol 123:366–374PubMedGoogle Scholar
  66. Kroesen BJ, McLaughlin PM, Schuilenga-Hut PH et al (2002) Tumor-targeted immune complex formation: effects on myeloid cell activation and tumor-directed immune cell migration. Int J Cancer 98:857–863PubMedGoogle Scholar
  67. Kumar S, Vinci JM, Pytel BA et al (1993) Expression of messenger RNAs for complement inhibitors in human tissues and tumors. Cancer Res 53:348–353PubMedGoogle Scholar
  68. Lett-Brown MA, Leonard EJ (1977) Histamine-induced inhibition of normal human basophil chemotaxis to C5a. J Immunol 118:815–818PubMedGoogle Scholar
  69. Liszewski MK, Fang CJ, Atkinson JP (2008) Inhibiting complement activation on cells at the step of C3 cleavage. Vaccine 26(suppl 8):I22–I27PubMedGoogle Scholar
  70. Liu J, Miwa T, Hilliard B et al (2005) The complement inhibitory protein DAF (CD55) suppresses T cell immunity in vivo. J Exp Med 201:567–577PubMedGoogle Scholar
  71. Loberg RD, Day LL, Dunn R et al (2006) Inhibition of decay-accelerating factor (CD55) attenuates prostate cancer growth and survival in vivo. Neoplasia 8:69–78PubMedGoogle Scholar
  72. Longhi MP, Sivasankar B, Omidvar N et al (2005) Cutting edge: murine CD59a modulates antiviral CD4+ T cell activity in a complement-independent manner. J Immunol 175:7098–7102PubMedGoogle Scholar
  73. Longhi MP, Harris CL, Morgan BP et al (2006) Holding T cells in check—a new role for complement regulators? Trends Immunol 27:102–108PubMedGoogle Scholar
  74. Lucas SD, Karlsson-Parra A, Nilsson B et al (1996) Tumor-specific deposition of immunoglobulin G and complement in papillary thyroid carcinoma. Hum Pathol 27:1329–1335PubMedGoogle Scholar
  75. Macor P, Tripodo C, Zorzet S et al (2007) In vivo targeting of human neutralizing antibodies against CD55 and CD59 to lymphoma cells increases the antitumor activity of rituximab. Cancer Res 67:10556–10563PubMedGoogle Scholar
  76. Manches O, Lui G, Chaperot L et al (2003) In vitro mechanisms of action of rituximab on primary non-Hodgkin lymphomas. Blood 101:949–954PubMedGoogle Scholar
  77. Manderson A, Pickering M, Botto M et al (2001) Continual low-level activation of the classical complement pathway. J Exp Med 194:747–756PubMedGoogle Scholar
  78. Marigo I, Bosio E, Solito S et al (2010) Tumor-induced tolerance and immune suppression depend on the C/EBPbeta transcription factor. Immunity 32:790–802PubMedGoogle Scholar
  79. Markiewski MM, DeAngelis RA, Benencia F et al (2008) Modulation of the antitumor immune response by complement. Nat Immunol 9:1225–1235PubMedGoogle Scholar
  80. Meri S, Morgan BP, Davies A et al (1990) Human protectin (CD59), an 18,000–20,000 MW complement lysis restricting factor, inhibits C5b-8 catalysed insertion of C9 into lipid bilayers. Immunology 71:1–9PubMedGoogle Scholar
  81. Meri S, Vakeva A, Laari T et al (1991) Soluble forms of CD59-antigen: distribution in body fluids and functional activity. Comp Inflam 8:193Google Scholar
  82. Meri S, Lehto T, Sutton CW et al (1996) Structural composition and functional characterization of soluble CD59: heterogeneity of the oligosaccharide and glycophosphoinositol (GPI) anchor revealed by laser-desorption mass spectrometric analysis. Biochem J 316(Pt 3):923–935PubMedGoogle Scholar
  83. Minta JO, Fung M, Turner S et al (1998) Cloning and characterization of the promoter for the human complement factor I (C3b/C4b inactivator) gene. Gene 208:17–24PubMedGoogle Scholar
  84. Mizuno M, Nakagawa M, Uesu T et al (1995) Detection of decay-accelerating factor in stool specimens of patients with colorectal cancer. Gastroenterology 109:826–831PubMedGoogle Scholar
  85. Morgan BP (1992) Effects of the membrane attack complex of complement on nucleated cells. Curr Top Microbiol Immunol 178:115–140PubMedGoogle Scholar
  86. Moskovich O, Fishelson Z (2007) Live cell imaging of outward and inward vesiculation induced by the complement c5b-9 complex. J Biol Chem 282:29977–29986PubMedGoogle Scholar
  87. Murray EW, Robbins SM (1998) Antibody cross-linking of the glycosylphosphatidylinositol-linked protein CD59 on hematopoietic cells induces signaling pathways resembling activation by complement. J Biol Chem 273:25279–25284PubMedGoogle Scholar
  88. Nagasawa S, Ichihara C, Stroud RM (1980) Cleavage of C4b by C3b inactivator: production of a nicked form of C4b, C4b′, as an intermediate cleavage product of C4b by C3b inactivator. J Immunol 125:578–582PubMedGoogle Scholar
  89. Nakano Y, Sumida K, Kikuta N et al (1992) Complete determination of disulfide bonds localized within the short consensus repeat units of decay accelerating factor (CD55 antigen). Biochim Biophys Acta 1116:235–240PubMedGoogle Scholar
  90. Nataf S, Davoust N, Ames RS et al (1999) Human T cells express the C5a receptor and are chemoattracted to C5a. J Immunol 162:4018–4023PubMedGoogle Scholar
  91. Natsume A, Niwa R, Satoh M (2009) Improving effector functions of antibodies for cancer treatment: enhancing ADCC and CDC. Drug Des Devel Ther 3:7–16PubMedGoogle Scholar
  92. Nicholson-Weller A, Halperin JA (1993) Membrane signaling by complement C5b-9, the membrane attack complex. Immunol Res 12:244–257PubMedGoogle Scholar
  93. Niculescu F, Rus HG, Retegan M et al (1992) Persistent complement activation on tumor cells in breast cancer. Am J Pathol 140:1039–1043PubMedGoogle Scholar
  94. Niehans GA, Cherwitz DL, Staley NA et al (1996) Human carcinomas variably express the complement inhibitory proteins CD46 (membrane cofactor protein), CD55 (decay-accelerating factor), and CD59 (protectin). Am J Pathol 149:129–142PubMedGoogle Scholar
  95. Nielsen CH, Antonsen S, Matthiesen SH et al (1997a) The roles of complement receptors type 1 (CR1, CD35) and type 3 (CR3, CD11b/CD18) in the regulation of the immune complex-elicited respiratory burst of polymorphonuclear leukocytes in whole blood. Eur J Immunol 27:2914–2919PubMedGoogle Scholar
  96. Nielsen CH, Matthiesen SH, Lyng I et al (1997b) The role of complement receptor type 1 (CR1, CD35) in determining the cellular distribution of opsonized immune complexes between whole blood cells: kinetic analysis of the buffering capacity of erythrocytes. Immunology 90:129–137PubMedGoogle Scholar
  97. Ollert MW, Kadlec JV, David K et al (1994) Antibody-mediated complement activation on nucleated cells. A quantitative analysis of the individual reaction steps. J Immunol 153:2213–2221PubMedGoogle Scholar
  98. Ottonello L, Corcione A, Tortolina G et al (1999) rC5a directs the in vitro migration of human memory and naive tonsillar B lymphocytes: implications for B cell trafficking in secondary lymphoid tissues. J Immunol 162:6510–6517PubMedGoogle Scholar
  99. Pilzer D, Gasser O, Moskovich O et al (2005) Emission of membrane vesicles: roles in complement resistance, immunity and cancer. Springer Semin Immunopathol 27:375–387PubMedGoogle Scholar
  100. Purcell DF, Deacon N, Andrew SM et al (1990) Human non-lineage antigen, CD46 (HuLy-m5): purification and partial sequencing demonstrates structural homology with complement-regulating glycoproteins. Immunogenetics 31:21–28PubMedGoogle Scholar
  101. Reff ME, Carner K, Chambers KS et al (1994) Depletion of B cells in vivo by a chimeric mouse human monoclonal antibody to CD20. Blood 83:435–445PubMedGoogle Scholar
  102. Reiter Y, Fishelson Z (1989a) Killing of human tumor cells by antibody C3b conjugates and human complement. Targeted Diagn Ther 2:119–135PubMedGoogle Scholar
  103. Reiter Y, Fishelson Z (1989b) Targeting of complement to tumor cells by heteroconjugates composed of antibodies and of the complement component C3b. J Immunol 142:2771–2777PubMedGoogle Scholar
  104. Ripoche J, Day AJ, Harris TJ et al (1988) The complete amino acid sequence of human complement factor H. Biochem J 249:593–602PubMedGoogle Scholar
  105. Ross GD, Lambris JD, Cain JA et al (1982) Generation of three different fragments of bound C3 with purified factor I or serum. I. Requirements for factor H vs CR1 cofactor activity. J Immunol 129:2051–2060PubMedGoogle Scholar
  106. Rus HG, Niculescu F, Shin ML (1996) Sublytic complement attack induces cell cycle in oligodendrocytes. J Immunol 156:4892–4900PubMedGoogle Scholar
  107. Rus HG, Niculescu FI, Shin ML (2001) Role of the C5b–9 complement complex in cell cycle and apoptosis. Immunol Rev 180:49–55PubMedGoogle Scholar
  108. Santoro F, Greenstone HL, Insinga A et al (2003) Interaction of glycoprotein H of human herpesvirus 6 with the cellular receptor CD46. J Biol Chem 278:25964–25969PubMedGoogle Scholar
  109. Scharfstein J, Ferreira A, Gigli I et al (1978) Human C4-binding protein. I. Isolation and characterization. J Exp Med 148:207–222PubMedGoogle Scholar
  110. Segerman A, Atkinson JP, Marttila M et al (2003) Adenovirus type 11 uses CD46 as a cellular receptor. J Virol 77:9183–9191PubMedGoogle Scholar
  111. Shafren DR, Bates RC, Agrez MV et al (1995) Coxsackieviruses B1, B3, and B5 use decay accelerating factor as a receptor for cell attachment. J Virol 69:3873–3877PubMedGoogle Scholar
  112. Shi XX, Zhang B, Zang JL et al (2009) CD59 silencing via retrovirus-mediated RNA interference enhanced complement-mediated cell damage in ovary cancer. Cell Mol Immunol 6:61–66PubMedGoogle Scholar
  113. Sim RB, DiScipio RG (1982) Purification and structural studies on the complement-system control protein beta 1H (Factor H). Biochem J 205:285–293PubMedGoogle Scholar
  114. Sivasankar B, Longhi MP, Gallagher KM et al (2009) CD59 blockade enhances antigen-specific CD4+ T cell responses in humans: a new target for cancer immunotherapy? J Immunol 182:5203–5207PubMedGoogle Scholar
  115. Smith BO, Mallin RL, Krych-Goldberg M et al (2002) Structure of the C3b binding site of CR1 (CD35), the immune adherence receptor. Cell 108:769–780PubMedGoogle Scholar
  116. Sokoloff MH, Nardin A, Solga MD et al (2000) Targeting of cancer cells with monoclonal antibodies specific for C3b(i). Cancer Immunol Immunother 49:551–562PubMedGoogle Scholar
  117. Spiridon CI, Ghetie MA, Uhr J et al (2002) Targeting multiple Her-2 epitopes with monoclonal antibodies results in improved antigrowth activity of a human breast cancer cell line in vitro and in vivo. Clin Cancer Res 8:1720–1730PubMedGoogle Scholar
  118. Spitzer D, Mitchell L, Atkinson J et al (2007) Properdin can initiate complement activation by binding specific target surfaces and providing a platform for de novo convertase assembly. J Immunol 179:2600–2608PubMedGoogle Scholar
  119. Sugita Y, Nakano Y, Oda E et al (1993) Determination of carboxyl-terminal residue and disulfide bonds of MACIF (CD59), a glycosyl-phosphatidylinositol-anchored membrane protein. J Biochem 114:473–477PubMedGoogle Scholar
  120. Tedesco F, Pausa M, Nardon E et al (1997) The cytolytically inactive terminal complement complex activates endothelial cells to express adhesion molecules and tissue factor procoagulant activity. J Exp Med 185:1619–1627PubMedGoogle Scholar
  121. Tediose T, Kolev M, Sivasankar B et al (2010) Interplay between REST and nucleolin transcription factors: a key mechanism in the overexpression of genes upon increased phosphorylation. Nucleic Acids Res 38:2799–2812Google Scholar
  122. Thiel S (2007) Complement activating soluble pattern recognition molecules with collagen-like regions, mannan-binding lectin, ficolins and associated proteins. Mol Immunol 44:3875–3888PubMedGoogle Scholar
  123. Thorsteinsson L, O’Dowd GM, Harrington PM et al (1998) The complement regulatory proteins CD46 and CD59, but not CD55, are highly expressed by glandular epithelium of human breast and colorectal tumour tissues. APMIS 106:869–878PubMedGoogle Scholar
  124. Treon SP, Mitsiades C, Mitsiades N et al (2001) Tumor cell expression of CD59 is associated with resistance to CD20 serotherapy in patients with B-cell malignancies. J Immunother 24:263–271Google Scholar
  125. Varela JC, Imai M, Atkinson C et al (2008) Modulation of protective T cell immunity by complement inhibitor expression on tumor cells. Cancer Res 68:6734–6742PubMedGoogle Scholar
  126. Vetvicka V, Thornton BP, Wieman TJ et al (1997) Targeting of natural killer cells to mammary carcinoma via naturally occurring tumor cell-bound iC3b and beta-glucan-primed CR3 (CD11b/CD18). J Immunol 159:599–605PubMedGoogle Scholar
  127. Walport MJ (2001a) Complement. First of two parts. N Engl J Med 344:1058–1066PubMedGoogle Scholar
  128. Walport MJ (2001b) Complement. Second of two parts. N Engl J Med 344:1140–1144PubMedGoogle Scholar
  129. Wang SY, Weiner G (2008) Complement and cellular cytotoxicity in antibody therapy of cancer. Expert Opin Biol Ther 8:759–768PubMedGoogle Scholar
  130. Ward T, Pipkin PA, Clarkson NA et al (1994) Decay-accelerating factor CD55 is identified as the receptor for echovirus 7 using CELICS, a rapid immuno-focal cloning method. EMBO J 13:5070–5074PubMedGoogle Scholar
  131. Weiner LM, Surana R, Wang S (2010) Monoclonal antibodies: versatile platforms for cancer immunotherapy. Nat Rev Immunol 10:317–327PubMedGoogle Scholar
  132. Yan J, Vetvicka V, Xia Y et al (1999) Beta-glucan, a “specific” biologic response modifier that uses antibodies to target tumors for cytotoxic recognition by leukocyte complement receptor type 3 (CD11b/CD18). J Immunol 163:3045–3052PubMedGoogle Scholar
  133. Yan J, Allendorf DJ, Li B et al (2008) The role of membrane complement regulatory proteins in cancer immunotherapy. Adv Exp Med Biol 632:159–174PubMedGoogle Scholar
  134. Ytting H, Jensenius JC, Christensen IJ et al (2004) Increased activity of the mannan-binding lectin complement activation pathway in patients with colorectal cancer. Scand J Gastroenterol 39:674–679PubMedGoogle Scholar
  135. Yu J, Dong S, Rushmere NK et al (1997) Mapping the regions of the complement inhibitor CD59 responsible for its species selective activity. Biochemistry 36:9423–9428PubMedGoogle Scholar
  136. Zell S, Geis N, Rutz R et al (2007) Down-regulation of CD55 and CD46 expression by anti-sense phosphorothioate oligonucleotides (S-ODNs) sensitizes tumour cells to complement attack. Clin Exp Immunol 150:576–584PubMedGoogle Scholar
  137. Zhou X, Hu W, Qin X (2008) The role of complement in the mechanism of action of rituximab for B-cell lymphoma: implications for therapy. Oncologist 13:954–966PubMedGoogle Scholar
  138. Ziller F, Macor P, Bulla R et al (2005) Controlling complement resistance in cancer by using human monoclonal antibodies that neutralize complement-regulatory proteins CD55 and CD59. Eur J Immunol 35:2175–2183PubMedGoogle Scholar
  139. Zipfel PF, Skerka C (2009) Complement regulators and inhibitory proteins. Nat Rev Immunol 9:729–740PubMedGoogle Scholar

Copyright information

© L. Hirszfeld Institute of Immunology and Experimental Therapy, Wroclaw, Poland 2011

Authors and Affiliations

  1. 1.Department of Infection, Immunity and Biochemistry, School of MedicineCardiff UniversityCardiffUK
  2. 2.Institute of Life Science, College of MedicineSwansea UniversitySwanseaUK

Personalised recommendations