Therapeutic antibodies directed at G protein-coupled receptors

mAbs

Volumn 2, Issue 6, 2010, Pages 594-606

  Hutchings, Catherine J ^a   Koglin, Markus ^a   Marshall, Fiona H ^a  

^a Heptares Therapeutics Ltd   (United Kingdom)

Author keywords

Chemokine receptor; Extracellular domain; Extracellular loop; G protein coupled receptor; Transmembrane spanning domain

Indexed keywords

ADHESION RECEPTOR; ALX 0651; AMG 761; CHEMOKINE RECEPTOR ANTAGONIST; CHEMOKINE RECEPTOR CXCR4; COMPLEMENT COMPONENT C5A RECEPTOR; FRIZZLED PROTEIN; G PROTEIN COUPLED RECEPTOR; KW 0761; MDX 1338; MEMBRANE RECEPTOR; METABOTROPIC RECEPTOR; MLN 1202; MU OPIATE RECEPTOR; NEUTRAZUMAB; PLERIXAFOR; RHODOPSIN; SECRETIN; UNCLASSIFIED DRUG;

ACUTE GRANULOCYTIC LEUKEMIA; ALLERGIC RHINITIS; ASTHMA; ATHEROSCLEROSIS; BINDING SITE; CELL MEMBRANE; CLINICAL TRIAL; DRUG BINDING; DRUG MECHANISM; HIGH THROUGHPUT SCREENING; HUMAN; HUMAN IMMUNODEFICIENCY VIRUS INFECTION; LIGAND BINDING; LUPUS VULGARIS; MULTIPLE SCLEROSIS; OLFACTORY RECEPTOR; PROTEIN EXPRESSION; PROTEIN TARGETING; REVIEW; RHEUMATOID ARTHRITIS; SENSORY RECEPTOR;

ANIMALS; ANTIBODIES; DRUG DISCOVERY; HUMANS; RECEPTORS, G-PROTEIN-COUPLED;

EID: 78649681781     PISSN: 19420862     EISSN: None     Source Type: Journal    
DOI: 10.4161/mabs.2.6.13420     Document Type: Review

References (113)

1. Foord SM, Bonner TI, Neubig RR, Rosser EM, Pin JP, Davenport AP, et al. International Union of Pharmacology. XLVI. G protein-coupled receptor list. Pharmacol Rev 2005; 57:279-88.
2. Lagerstrom MC, Schioth HB. Structural diversity of G protein-coupled receptors and significance for drug discovery. Nat Rev Drug Discov 2008; 7:339-57.
3. Tyndall JD, Sandilya R. GPCR agonists and antagonists in the clinic. Med Chem 2005; 1:405-21.
4. Pin JP, Kniazeff J, Goudet C, Bessis AS, Liu J, Galvez T, et al. The activation mechanism of class-C G-protein coupled receptors. Biol Cell 2004; 96:335-42. (Pubitemid 38807898)
5. Reichert JM, Rosensweig CJ, Faden LB, Dewitz MC. Monoclonal antibody successes in the clinic. Nat Biotechnol 2005; 23:1073-8.
6. Macarron R. Critical review of the role of HTS in drug discovery. Drug Discov Today 2006; 11:277-9.
7. Bymaster FP, Calligaro DO, Falcone JF, Marsh RD, Moore NA, Tye NC, et al. Radioreceptor binding profile of the atypical antipsychotic olanzapine. Neuropsychopharmacology 1996; 14:87-96.
8. Pradidarcheep W, Stallen J, Labruyere WT, Dabhoiwala NF, Michel MC, Lamers WH. Lack of specificity of commercially available antisera against muscarinergic and adrenergic receptors. Naunyn Schmiedebergs Arch Pharmacol 2009; 379:397-402.
9. Hamdani N, van der Velden J. Lack of specificity of antibodies directed against human beta-adrenergic receptors. Naunyn Schmiedebergs Arch Pharmacol 2009; 379:403-7.
10. Jeffrey P, Summerfield S. Assessment of the blood-brain barrier in CNS drug discovery. Neurobiol Dis 2010; 37:33-7.
11. Stein C, Lang LJ. Peripheral mechanisms of opioid analgesia. Curr Opin Pharmacol 2009; 9:3-8.
12. Welch MJ, Meltzer EO, Simons FE. H1-antihistamines and the central nervous system. Clin Allergy Immunol 2002; 17:337-88.
13. Agarwal N, Pacher P, Tegeder I, Amaya F, Constantin CE, Brenner GJ, et al. Cannabinoids mediate analgesia largely via peripheral type 1 cannabinoid receptors in nociceptors. Nat Neurosci 2007; 10:870-9.
14. Nogueiras R, Veyrat-Durebex C, Suchanek PM, Klein M, Tschop J, Caldwell C, et al. Peripheral, but not central, CB1 antagonism provides food intake-independent metabolic benefits in diet-induced obese rats. Diabetes 2008; 57:2977-91.
15. Deshpande DA, Penn RB. Targeting G protein-coupled receptor signaling in asthma. Cell Signal 2006; 18:2105-20.
16. Dorsam RT, Gutkind JS. G-protein-coupled receptors and cancer. Nat Rev Cancer 2007; 7:79-94.
17. Montaner S, Sodhi A, Ramsdell AK, Martin D, Hu J, Sawai ET, et al. The Kaposi's sarcoma-associated herpesvirus G protein-coupled receptor as a therapeutic target for the treatment of Kaposi's sarcoma. Cancer Res 2006; 66:168-74.
18. de Jong M, Breeman WA, Kwekkeboom DJ, Valkema R, Krenning EP. Tumor imaging and therapy using radiolabeled somatostatin analogues. Acc Chem Res 2009; 42:873-80.
19. Balkwill F. Cancer and the chemokine network. Nat Rev Cancer 2004; 4:540-50.
20. Richard DE, Vouret-Craviari V, Pouyssegur J. Angiogenesis and G-protein-coupled receptors: signals that bridge the gap. Oncogene 2001; 20:1556-62.
21. Horuk R. Chemokine receptor antagonists: overcoming developmental hurdles. Nat Rev Drug Discov 2009; 8:23-33.
22. Graler MH, Goetzl EJ. Lysophospholipids and their G protein-coupled receptors in inflammation and immunity. Biochim Biophys Acta 2002; 1582:168-74.
23. Hancock WW. Chemokines and transplant immunobiology. J Am Soc Nephrol 2002; 13:821-4.
24. Gao W, Faia KL, Csizmadia V, Smiley ST, Soler D, King JA, et al. Beneficial effects of targeting CCR5 in allograft recipients. Transplantation 2001; 72:1199-205.
25. Das AM, Brodmerkel CM. Chemokines and chemokine receptors: Large and small therapeutic strategies for inflammatory diseases. Drug Discovery Today: Therapeutic Strategies 2006; 3:381-8.
26. Winzell MS, Ahren B. G-protein-coupled receptors and islet function-implications for treatment of type 2 diabetes. Pharmacol Ther 2007; 116:437-48.
27. Brown AJ, Goldsworthy SM, Barnes AA, Eilert MM, Tcheang L, Daniels D, et al. The Orphan G protein-coupled receptors GPR41 and GPR43 are activated by propionate and other short chain carboxylic acids. J Biol Chem 2003; 278:11312-9.
28. Overton HA, Babbs AJ, Doel SM, Fyfe MC, Gardner LS, Griffin G, et al. Deorphanization of a G protein-coupled receptor for oleoylethanolamide and its use in the discovery of small-molecule hypophagic agents. Cell Metab 2006; 3:167-75.
29. Hirasawa A, Tsumaya K, Awaji T, Katsuma S, Adachi T, Yamada M, et al. Free fatty acids regulate gut incretin glucagon-like peptide-1 secretion through GPR120. Nat Med 2005; 11:90-4.
30. McCusker EC, Bane SE, O'Malley MA, Robinson AS. Heterologous GPCR expression: a bottleneck to obtaining crystal structures. Biotechnol Prog 2007; 23:540-7.
31. Grisshammer R. Purification of recombinant G-protein-coupled receptors. Methods Enzymol 2009; 463:631-45.
32. Baribaud F, Edwards TG, Sharron M, Brelot A, Heveker N, Price K, et al. Antigenically distinct conformations of CXCR4. J Virol 2001; 75:8957-67.
33. Carnec X, Quan L, Olson WC, Hazan U, Dragic T. Anti-CXCR4 monoclonal antibodies recognizing overlapping epitopes differ significantly in their ability to inhibit entry of human immunodeficiency virus type 1. J Virol 2005; 79:1930-3.
34. Sloane AJ, Raso V, Dimitrov DS, Xiao X, Deo S, Muljadi N, et al. Marked structural and functional heterogeneity in CXCR4: separation of HIV-1 and SDF-1alpha responses. Immunol Cell Biol 2005; 83:129-43.
35. Farzan M, Mirzabekov T, Kolchinsky P, Wyatt R, Cayabyab M, Gerard NP, et al. Tyrosine sulfation of the amino terminus of CCR5 facilitates HIV-1 entry. Cell 1999; 96:667-76.
36. Lapidot T, Petit I. Current understanding of stem cell mobilization: the roles of chemokines, proteolytic enzymes, adhesion molecules, cytokines and stromal cells. Exp Hematol 2002; 30:973-81.
37. Kenakin T. Principles: receptor theory in pharmacology. Trends Pharmacol Sci 2004; 25:186-92.
38. Hipser C, Bushlin I, Gupta A, Gomes I, Devi LA. Role of antibodies in developing drugs that target G-protein-coupled receptor dimers. Mt Sinai J Med 2010; 77:374-80.
39. Gupta A, Mulder J, Gomes I, Rozenfeld R, Bushlin I, Ong E, et al. Increased abundance of opioid receptor heteromers after chronic morphine administration. Sci Signal 2010; 3:54.
40. Kirkpatrick P. Specificity concerns with antibodies for receptor mapping. Nat Rev Drug Discov 2009; 8:278.
41. Bodei S, Arrighi N, Spano P, Sigala S. Should we be cautious on the use of commercially available antibodies to dopamine receptors? Naunyn Schmiedebergs Arch Pharmacol 2009; 379:413-5.
42. Jensen BC, Swigart PM, Simpson PC. Ten commercial antibodies for alpha-1-adrenergic receptor subtypes are nonspecific. Naunyn Schmiedebergs Arch Pharmacol 2009; 379:409-12.
43. Lu X, Bartfai T. Analyzing the validity of GalR1 and GalR2 antibodies using knockout mice. Naunyn Schmiedebergs Arch Pharmacol 2009; 379:417-20.
44. Gupta A, Decaillot FM, Gomes I, Tkalych O, Heimann AS, Ferro ES, et al. Conformation state-sensitive antibodies to G-protein-coupled receptors. J Biol Chem 2007; 282:5116-24.
45. Lebesgue D, Wallukat G, Mijares A, Granier C, Argibay J, Hoebeke J. An agonist-like monoclonal antibody against the human beta2-adrenoceptor. Eur J Pharmacol 1998; 348:123-33.
46. Sasaki Y, Kosaka H, Usami K, Toki H, Kawai H, Shiraishi N, et al. Establishment of a novel monoclonal antibody against LGR5. Biochem Biophys Res Commun 2010; 394:498-502.
47. Huang L, Sato AK, Sachdeva M, Fleming T, Townsend S, Dransfield DT. Discovery of human antibodies against the C5aR target using phage display technology. J Mol Recognit 2005; 18:327-33.
48. Hawlisch H, Frank R, Hennecke M, Baensch M, Sohns B, Arseniev L, et al. Site-directed C3a receptor antibodies from phage display libraries. J Immunol 1998; 160:2947-58.
49. Chain BM, Noursadeghi M, Gardener M, Tsang J, Wright E. HIV blocking antibodies following immunisation with chimaeric peptides coding a short N-terminal sequence of the CCR5 receptor. Vaccine 2008; 26:5752-9.
50. Li YY, Hou TJ, Goddard WA, 3rd. Computational modeling of structure-function of g protein-coupled receptors with applications for drug design. Curr Med Chem 2010; 17:1167-80.
51. Timmerman P, Puijk WC, Meloen RH. Functional reconstruction and synthetic mimicry of a conformational epitope using CLIPS technology. J Mol Recognit 2007; 20:283-99.
52. Misumi S, Nakayama D, Kusaba M, Iiboshi T, Mukai R, Tachibana K, et al. Effects of immunization with CCR5-based cycloimmunogen on simian/ HIVSF162P3 challenge. J Immunol 2006; 176:463-71.
53. Zhang Y, Pool C, Sadler K, Yan HP, Edl J, Wang X, et al. Selection of active ScFv to G-protein-coupled receptor CCR5 using surface antigen-mimicking peptides. Biochemistry 2004; 43:12575-84.
54. Sommerfelt MA. Circular CCR5 peptide conjugates and uses thereof (WO2008074895). Expert Opin Ther Pat 2009; 19:1323-8.
55. Spohn G, Bachmann MF. Exploiting viral properties for the rational design of modern vaccines. Expert Rev Vaccines 2008; 7:43-54.
56. Chackerian B, Durfee MR, Schiller JT. Virus-like display of a neo-self antigen reverses B cell anergy in a B cell receptor transgenic mouse model. J Immunol 2008; 180:5816-25.
57. Hunter Z, Smyth HD, Durfee P, Chackerian B. Induction of mucosal and systemic antibody responses against the HIV coreceptor CCR5 upon intramuscular immunization and aerosol delivery of a virus-like particle based vaccine. Vaccine 2009; 28:403-14.
58. Yan H, Gu W, Yang J, Bi V, Shen Y, Lee E, et al. Fully human monoclonal antibodies antagonizing the glucagon receptor improve glucose homeostasis in mice and monkeys. J Pharmacol Exp Ther 2009; 329:102-11.
59. Lau YY, Ma P, Gibiansky L, Komorowski R, Wang J, Wang G, et al. Pharmacokinetic and pharmacodynamic modeling of a monoclonal antibody antagonist of glucagon receptor in male ob/ob mice. AAPS J 2009; 11:700-9.
60. Ohno Y, Suda K, Masuko K, Yagi H, Hashimoto Y, Masuko T. Production and characterization of highly tumor-specific rat monoclonal antibodies recognizing the extracellular domain of human L-type amino-acid transporter 1. Cancer Sci 2008; 99:1000-7.
61. Graeler M, Shankar G, Goetzl EJ. Cutting edge: suppression of T cell chemotaxis by sphingosine 1-phosphate. J Immunol 2002; 169:4084-7.
62. Goetzl EJ, Dembrow D, Van Brocklyn JR, Graler M, Huang MC. An IgM-kappa rat monoclonal antibody specific for the type 1 sphingosine 1-phosphate G protein-coupled receptor with antagonist and agonist activities. Immunol Lett 2004; 93:63-9.
63. Breckpot K, Escors D. Dendritic cells for active anticancer immunotherapy: targeting activation pathways through genetic modification. Endocr Metab Immune Disord Drug Targets 2009; 9:328-43.
64. Tamura T, Chiba J. Production of antibodies against multipass membrane proteins expressed in human tumor cells using dendritic cell immunization. J Biomed Biotechnol 2009; 2009:673098.
65. Colino J, Snapper CM. Exosomes from bone marrow dendritic cells pulsed with diphtheria toxoid preferentially induce type 1 antigen-specific IgG responses in naive recipients in the absence of free antigen. J Immunol 2006; 177:3757-62. (Pubitemid 44359908)
66. Thery C, Regnault A, Garin J, Wolfers J, Zitvogel L, Ricciardi-Castagnoli P, et al. Molecular characterization of dendritic cell-derived exosomes. Selective accumulation of the heat shock protein hsc73. J Cell Biol 1999; 147:599-610.
67. Morse MA, Garst J, Osada T, Khan S, Hobeika A, Clay TM, et al. A phase I study of dexosome immunotherapy in patients with advanced non-small cell lung cancer. J Transl Med 2005; 3:9.
68. Escudier B, Dorval T, Chaput N, Andre F, Caby MP, Novault S, et al. Vaccination of metastatic melanoma patients with autologous dendritic cell (DC) derived-exosomes: results of the first phase I clinical trial. J Transl Med 2005; 3:10.
69. Thery C, Zitvogel L, Amigorena S. Exosomes: composition, biogenesis and function. Nat Rev Immunol 2002; 2:569-79.
70. Delcayre A, Shu H, Le Pecq JB. Dendritic cell-derived exosomes in cancer immunotherapy: exploiting nature's antigen delivery pathway. Expert Rev Anticancer Ther 2005; 5:537-47.
71. Estelles A, Sperinde J, Roulon T, Aguilar B, Bonner C, LePecq JB, et al. Exosome nanovesicles displaying G protein-coupled receptors for drug discovery. Int J Nanomedicine 2007; 2:751-60.
72. Loisel TP, Ansanay H, St-Onge S, Gay B, Boulanger P, Strosberg AD, et al. Recovery of homogeneous and functional beta2-adrenergic receptors from extracellular baculovirus particles. Nat Biotechnol 1997; 15:1300-4.
73. Lee B, Sharron M, Montaner LJ, Weissman D, Doms RW. Quantification of CD4, CCR5, and CXCR4 levels on lymphocyte subsets, dendritic cells and differentially conditioned monocyte-derived macrophages. Proc Natl Acad Sci USA 1999; 96:5215-20.
74. Gu W, Yan H, Winters KA, Komorowski R, Vonderfecht S, Atangan L, et al. Long-term inhibition of the glucagon receptor with a monoclonal antibody in mice causes sustained improvement in glycemic control, with reversible alpha-cell hyperplasia and hyperglucagonemia. J Pharmacol Exp Ther 2009; 331:871-81.
75. Freson K, Peeters K, De Vos R, Wittevrongel C, Thys C, Hoylaerts MF, et al. PACAP and its receptor VPAC1 regulate megakaryocyte maturation: therapeutic implications. Blood 2008; 111:1885-93.
76. Robertson N, Jazayeri A, Errey J, Baig A, Hurrell E, Zhukov A, et al. The properties of thermostabilised G protein-coupled receptors (StaRs) and their use in drug discovery. Neuropharmacology 2010; In press.
77. 1-adrenergic receptor in a detergent-resistant form. Proc Natl Acad Sci USA 2008; 105:877-82.
78. 2a receptor. Proc Natl Acad Sci USA 2008; 105:10744-9.
79. Shibata Y, White JF, Serrano-Vega MJ, Magnani F, Aloia AL, Grisshammer R, et al. Thermostabilization of the neurotensin receptor NTS1. J Mol Biol 2009; 390:262-77.
80. Bokoch MP, Zou Y, Rasmussen SG, Liu CW, Nygaard R, Rosenbaum DM, et al. Ligand-specific regulation of the extracellular surface of a G-protein-coupled receptor. Nature 2010; 463:108-12.
81. Day PW, Rasmussen SG, Parnot C, Fung JJ, Masood A, Kobilka TS, et al. A monoclonal antibody for G protein-coupled receptor crystallography. Nat Methods 2007; 4:927-9.
82. Jorissen H, Bektas N, Dahl E, Hartmann A, ten Haaf A, Di Fiore S, et al. Production and characterisation of monoclonal antibodies against RAI3 and its expression in human breast cancer. BMC Cancer 2009; 9:200.
83. Xu C, Sui J, Tao H, Zhu Q, Marasco WA. Human anti-CXCR4 antibodies undergo VH replacement, exhibit functional V-region sulfation and define CXCR4 antigenic heterogeneity. J Immunol 2007; 179:2408-18.
84. Mirzabekov T, Kontos H, Farzan M, Marasco W, Sodroski J. Paramagnetic proteoliposomes containing a pure, native and oriented seven-transmembrane segment protein, CCR5. Nat Biotechnol 2000; 18:649-54.
85. Harding PJ, Attrill H, Boehringer J, Ross S, Wadhams GH, Smith E, et al. Constitutive dimerization of the G-protein coupled receptor, neurotensin receptor 1, reconstituted into phospholipid bilayers. Biophys J 2009; 96:964-73.
86. Whorton MR, Bokoch MP, Rasmussen SG, Huang B, Zare RN, Kobilka B, et al. A monomeric G protein-coupled receptor isolated in a high-density lipoprotein particle efficiently activates its G protein. Proc Natl Acad Sci USA 2007; 104:7682-7.
87. Yao XJ, Velez Ruiz G, Whorton MR, Rasmussen SG, DeVree BT, Deupi X, et al. The effect of ligand efficacy on the formation and stability of a GPCR-G protein complex. Proc Natl Acad Sci USA 2009; 106:9501-6.
88. Bhattacharya P, Grimme S, Ganesh B, Gopisetty A, Sheng JR, Martinez O, et al. Nanodisc-incorporated hemagglutinin provides protective immunity against influenza virus infection. J Virol 2010; 84:361-71.
89. Dahmane T, Damian M, Mary S, Popot JL, Banères JL. Amphipol-assisted in vitro folding of G proteincoupled receptors. Biochemistry 2009; 48:6516-21.
90. Elagoz A, Henderson D, Babu PS, Salter S, Grahames C, Bowers L, et al. A truncated form of CKbeta8-1 is a potent agonist for human formyl peptide-receptor-like 1 receptor. Br J Pharmacol 2004; 141:37-46.
91. Fujimoto A, Takatsuka S, Ishida I, Chiba J. Production of human antibodies to native cytokine receptors using the genetic immunization of KM mice. Hum Antibodies 2009; 18:75-80.
92. Kaptein SJ, Jungscheleger-Russell J, Martinez-Martinez P, Beisser PS, Lavreysen H, Vanheel A, et al. Generation of polyclonal antibodies directed against G protein-coupled receptors using electroporation-aided DNA immunization. J Pharmacol Toxicol Methods 2008; 58:27-31.
93. Kalinowska A, Losy J. Investigational C-C chemokine receptor 2 antagonists for the treatment of autoimmune diseases. Expert Opin Investig Drugs 2008; 17:1267-79.
94. Guo RF, Ward PA. Role of C5a in inflammatory responses. Annu Rev Immunol 2005; 23:821-52.
95. Lee H, Zahra D, Vogelzang A, Newton R, Thatcher J, Quan A, et al. Human C5aR knock-in mice facilitate the production and assessment of anti-inflammatory monoclonal antibodies. Nat Biotechnol 2006; 24:1279-84.
96. Muller A, Homey B, Soto H, Ge N, Catron D, Buchanan ME, et al. Involvement of chemokine receptors in breast cancer metastasis. Nature 2001; 410:50-6.
97. Guleng B, Tateishi K, Ohta M, Kanai F, Jazag A, Ijichi H, et al. Blockade of the stromal cell-derived factor-1/CXCR4 axis attenuates in vivo tumor growth by inhibiting angiogenesis in a vascular endothelial growth factor-independent manner. Cancer Res 2005; 65:5864-71.
98. Bertolini F, Dell'Agnola C, Mancuso P, Rabascio C, Burlini A, Monestiroli S, et al. CXCR4 neutralization, a novel therapeutic approach for non-Hodgkin's lymphoma. Cancer Res 2002; 62:3106-12.
99. Hendrix CW, Flexner C, MacFarland RT, Giandomenico C, Fuchs EJ, Redpath E, et al. Pharmacokinetics and safety of AMD-3100, a novel antagonist of the CXCR-4 chemokine receptor, in human volunteers. Antimicrob Agents Chemother 2000; 44:1667-73.
100. Proudfoot AE, Power CA, Schwarz MK. Antichemokine small molecule drugs: a promising future? Expert Opin Investig Drugs 2010; 19:345-55.
101. Conrad SM, Strauss-Ayali D, Field AE, Mack M, Mosser DM. Leishmania-derived murine monocyte chemoattractant protein 1 enhances the recruitment of restrictive population of CC chemokine receptor 2-positive macrophages. Infect Immun 2007; 75:653-65.
102. -/- mice reveals a role for chemokines in the initiation of atherosclerosis. Nature 1998; 394:894-7.
103. Lu Y, Chen Q, Corey E, Xie W, Fan J, Mizokami A, et al. Activation of MCP-1/CCR2 axis promotes prostate cancer growth in bone. Clin Exp Metastasis 2009; 26:161-9.
104. + stromal cells of monocytic origin to promote breast cancer metastasis to lung and bone. J Biol Chem 2009; 284:29087-96.
105. Xia M, Sui Z. Recent developments in CCR2 antagonists. Expert Opin Ther Pat 2009; 19:295-303.
106. Ribeiro S, Horuk R. The clinical potential of chemokine receptor antagonists. Pharmacol Ther 2005; 107:44-58.
107. Vergunst CE, Gerlag DM, Lopatinskaya L, Klareskog L, Smith MD, van den Bosch F, et al. Modulation of CCR2 in rheumatoid arthritis: a double-blind, randomized, placebo-controlled clinical trial. Arthritis Rheum 2008; 58:1931-9.
108. Ito A, Ishida T, Utsunomiya A, Sato F, Mori F, Yano H, et al. Defucosylated anti-CCR4 monoclonal antibody exerts potent ADCC against primary ATLL cells mediated by autologous human immune cells in NOD/Shi-scid, IL-2R gamma(null) mice in vivo. J Immunol 2009; 183:4782-91.
109. Ishii T, Ishida T, Utsunomiya A, Inagaki A, Yano H, Komatsu H, et al. Defucosylated humanized anti-CCR4 monoclonal antibody KW-0761 as a novel immunotherapeutic agent for adult T-cell leukemia/lymphoma. Clin Cancer Res 2010; 16:1520-31.
110. Ishida T, Utsunomiya A, Iida S, Inagaki H, Takatsuka Y, Kusumoto S, et al. Clinical significance of CCR4 expression in adult T-cell leukemia/lymphoma: its close association with skin involvement and unfavorable outcome. Clin Cancer Res 2003; 9:3625-34.
111. Yamamoto K, Utsunomiya A, Tobinai K, Tsukasaki K, Uike N, Uozumi K, et al. Phase I study of KW-0761, a defucosylated humanized anti-CCR4 antibody, in relapsed patients with adult T-cell leukemia-lymphoma and peripheral T-cell lymphoma. J Clin Oncol 2010; 28:1591-8.
112. Yano H, Ishida T, Imada K, Sakai T, Ishii T, Inagaki A, et al. Augmentation of antitumour activity of defucosylated chimeric anti-CCR4 monoclonal antibody in SCID mouse model of adult T-cell leukaemia/lymphoma using G-CSF. Br J Haematol 2008; 140:586-9.
113. Bettelli E, Korn T, Kuchroo VK. Th17: the third member of the effector T cell trilogy. Curr Opin Immunol 2007; 19:652-7.