CXCR4 nanobodies (VHH-based single variable domains) potently inhibit chemotaxis and HIV-1 replication and mobilize stem cells

Proceedings of the National Academy of Sciences of the United States of America

Volumn 107, Issue 47, 2010, Pages 20565-20570

  Jähnichen, Sven ^a   Blanchetot, Christophe ^b   Maussang, David ^a   Gonzalez Pajuelo, Maria ^c   Chow, Ken Y ^a   Bosch, Leontien ^a   De Vrieze, Sindi ^c   Serruys, Benedikte ^c   Ulrichts, Hans ^c   Vandevelde, Wesly ^c   Saunders, Michael ^c,e   De Haard, Hans J ^b,c   Schols, Dominique ^d   Leurs, Rob ^a   Vanlandschoot, Peter ^c   Verrips, Theo ^b   Smit, Martine J ^a  

^a VU UNIVERSITY AMSTERDAM   (Netherlands)

^b UTRECHT UNIVERSITY   (Netherlands)

^c ABLYNX NV   (Belgium)

^d REGA INSTITUTE FOR MEDICAL RESEARCH   (Belgium)

^e Bio Michs   (Belgium)

Author keywords

Chemotaxis; CXCR4 antagonist; HIV; Nanobody; Stem cell mobilization

Indexed keywords

CHEMOKINE RECEPTOR CXCR4; CHEMOKINE RECEPTOR CXCR4 ANTAGONIST; CHEMOKINE RECEPTOR CXCR4 NANOBODY; EPITOPE; PLERIXAFOR; STROMAL CELL DERIVED FACTOR 1; UNCLASSIFIED DRUG;

ANIMAL CELL; ANIMAL EXPERIMENT; ANTIVIRAL ACTIVITY; BINDING AFFINITY; CHEMOTAXIS; CONFERENCE PAPER; DRUG RECEPTOR BINDING; HUMAN; HUMAN CELL; HUMAN IMMUNODEFICIENCY VIRUS 1; MACACA FASCICULARIS; NONHUMAN; PRIORITY JOURNAL; SIGNAL TRANSDUCTION; STEM CELL MOBILIZATION; T LYMPHOCYTE; VIRUS REPLICATION;

HUMAN IMMUNODEFICIENCY VIRUS 1; MACACA FASCICULARIS;

EID: 78650573881     PISSN: 00278424     EISSN: 10916490     Source Type: Journal    
DOI: 10.1073/pnas.1012865107     Document Type: Article

References (50)

1. Overington JP, Al-Lazikani B, Hopkins AL (2006) How many drug targets are there? Nat Rev Drug Discov 5:993-996.
2. Gupta A, Heimann AS, Gomes I, Devi LA (2008) Antibodies against G-protein coupled receptors: Novel uses in screening and drug development. Comb Chem High Throughput Screen 11:463-467.
3. Harmsen MM, De Haard HJ (2007) Properties, production, and applications of camelid single-domain antibody fragments. Appl Microbiol Biotechnol 77:13-22.
4. De Genst E, et al. (2006) Molecular basis for the preferential cleft recognition by dromedary heavy-chain antibodies. Proc Natl Acad Sci USA 103:4586-4591.
5. Henderson KA, et al. (2007) Structure of an IgNAR-AMA1 complex: Targeting a conserved hydrophobic cleft broadens malarial strain recognition. Structure 15: 1452-1466.
6. Lauwereys M, et al. (1998) Potent enzyme inhibitors derived from dromedary heavychain antibodies. EMBO J 17:3512-3520.
7. Stijlemans B, et al. (2004) Efficient targeting of conserved cryptic epitopes of infectious agents by single domain antibodies. African trypanosomes as paradigm. J Biol Chem 279:1256-1261.
8. Van Bockstaele F, Holz JB, Revets H (2009) The development of nanobodies for therapeutic applications. Curr Opin Investig Drugs 10:1212-1224.
9. Gonzalo JA, et al. (2000) Critical involvement of the chemotactic axis CXCR4/stromal cell-derived factor-1 alpha in the inflammatory component of allergic airway disease. J Immunol 165:499-508.
10. Matthys P, et al. (2001) AMD3100, a potent and specific antagonist of the stromal cellderived factor-1 chemokine receptor CXCR4, inhibits autoimmune joint inflammation in IFN-gamma receptor-deficient mice. J Immunol 167:4686-4692.
11. Ratajczak MZ, et al. (2006) The pleiotropic effects of the SDF-1-CXCR4 axis in organogenesis, regeneration and tumorigenesis. Leukemia 20:1915-1924.
12. Burger JA, Kipps TJ (2006) CXCR4: a key receptor in the crosstalk between tumor cells and their microenvironment. Blood 107:1761-1767.
13. Feng Y, Broder CC, Kennedy PE, Berger EA (1996) HIV-1 entry cofactor: functional cDNA cloning of a seven-transmembrane, G protein-coupled receptor. Science 272: 872-877. (Pubitemid 26154590)
14. Liang X (2008) CXCR4, inhibitors and mechanisms of action. Chem Biol Drug Des 72: 97-110.
15. Hendrix CW, et al.; AMD3100 HIV Study Group (2004) Safety, pharmacokinetics, and antiviral activity of AMD3100, a selective CXCR4 receptor inhibitor, in HIV-1 infection. J Acquir Immune Defic Syndr 37:1253-1262.
16. Cashen AF (2009) Plerixafor hydrochloride: A novel agent for the mobilization of peripheral blood stem cells. Drugs Today (Barc) 45:497-505.
17. DiPersio JF, et al.; 3101 Investigators (2009) Phase III prospective randomized doubleblind placebo-controlled trial of plerixafor plus granulocyte colony-stimulating factor compared with placebo plus granulocyte colony-stimulating factor for autologous stem-cell mobilization and transplantation for patients with non-Hodgkin's lymphoma. J Clin Oncol 27:4767-4773.
18. DiPersio JF, et al.; 3102 Investigators (2009) Plerixafor and G-CSF versus placebo and G-CSF to mobilize hematopoietic stem cells for autologous stem cell transplantation in patients with multiple myeloma. Blood 113:5720-5726.
19. McKnight A, et al. (1997) Inhibition of human immunodeficiency virus fusion by a monoclonal antibody to a coreceptor (CXCR4) is both cell type and virus strain dependent. J Virol 71:1692-1696.
20. Müller A, et al. (2001) Involvement of chemokine receptors in breast cancer metastasis. Nature 410:50-56.
21. Ottaiano A, et al. (2005) Inhibitory effects of anti-CXCR4 antibodies on human colon cancer cells. Cancer Immunol Immunother 54:781-791.
22. Strizki JM, Turner JD, Collman RG, Hoxie J, González-Scarano F (1997) A monoclonal antibody (12G5) directed against CXCR-4 inhibits infection with the dual-tropic human immunodeficiency virus type 1 isolate HIV-1(89.6) but not the T-tropic isolate HIV-1(HxB). J Virol 71:5678-5683.
23. Vaday GG, et al. (2004) CXCR4 and CXCL12 (SDF-1) in prostate cancer: inhibitory effects of human single chain Fv antibodies. Clin Cancer Res 10:5630-5639.
24. Xu C, Sui J, Tao H, Zhu Q, Marasco WA (2007) Human anti-CXCR4 antibodies undergo VH replacement, exhibit functional V-region sulfation, and define CXCR4 antigenic heterogeneity. J Immunol 179:2408-2418.
25. Baribaud F, et al. (2001) Antigenically distinct conformations of CXCR4. J Virol 75: 8957-8967.
26. Carnec X, Quan L, Olson WC, Hazan U, Dragic T (2005) Anti-CXCR4 monoclonal antibodies recognizing overlapping epitopes differ significantly in their ability to inhibit entry of human immunodeficiency virus type 1. J Virol 79:1930-1933.
27. Coward P, Chan SD, Wada HG, Humphries GM, Conklin BR (1999) Chimeric G proteins allow a high-throughput signaling assay of Gi-coupled receptors. Anal Biochem 270: 242-248.
28. Levoye A, Balabanian K, Baleux F, Bachelerie F, Lagane B (2009) CXCR7 heterodimerizes with CXCR4 and regulates CXCL12-mediated G protein signaling. Blood 113:6085-6093.
29. Brelot A, Heveker N, Montes M, Alizon M (2000) Identification of residues of CXCR4 critical for human immunodeficiency virus coreceptor and chemokine receptor activities. J Biol Chem 275:23736-23744.
30. Kofuku Y, et al. (2009) Structural basis of the interaction between chemokine stromal cell-derived factor-1/CXCL12 and its G-protein-coupled receptor CXCR4. J Biol Chem 284:35240-35250.
31. Zhou N, et al. (2001) Structural and functional characterization of human CXCR4 as a chemokine receptor and HIV-1 co-receptor by mutagenesis and molecular modeling studies. J Biol Chem 276:42826-42833.
32. Paes C, et al. (2009) Atomic-level mapping of antibody epitopes on a GPCR. J Am Chem Soc 131:6952-6954.
33. Coppieters K, et al. (2006) Formatted anti-tumor necrosis factor alpha VHH proteins derived from camelids show superior potency and targeting to inflamed joints in a murine model of collagen-induced arthritis. Arthritis Rheum 54:1856-1866.
34. Roovers RC, et al. (2007) Efficient inhibition of EGFR signaling and of tumour growth by antagonistic anti-EFGR nanobodies. Cancer Immunol Immunother 56:303-317.
35. Zhang J, et al. (2004) Pentamerization of single-domain antibodies from phage libraries: a novel strategy for the rapid generation of high-avidity antibody reagents. J Mol Biol 335:49-56.
36. Zhang WB, et al. (2002) A point mutation that confers constitutive activity to CXCR4 reveals that T140 is an inverse agonist and that AMD3100 and ALX40-4C are weak partial agonists. J Biol Chem 277:24515-24521.
37. Wong RS, et al. (2008) Comparison of the potential multiple binding modes of bicyclam, monocylam, and noncyclam small-molecule CXC chemokine receptor 4 inhibitors. Mol Pharmacol 74:1485-1495.
38. Dalrymple MB, Pfleger KD, Eidne KA (2008) G protein-coupled receptor dimers: functional consequences, disease states and drug targets. Pharmacol Ther 118:359-371.
39. Prinster SC, Hague C, Hall RA (2005) Heterodimerization of g protein-coupled receptors: specificity and functional significance. Pharmacol Rev 57:289-298.
40. Babcock GJ, Farzan M, Sodroski J (2003) Ligand-independent dimerization of CXCR4, a principal HIV-1 coreceptor. J Biol Chem 278:3378-3385.
41. Lagane B, et al. (2008) CXCR4 dimerization and beta-arrestin-mediated signaling account for the enhanced chemotaxis to CXCL12 in WHIM syndrome. Blood 112: 34-44.
42. Wang J, He L, Combs CA, Roderiquez G, Norcross MA (2006) Dimerization of CXCR4 in living malignant cells: Control of cell migration by a synthetic peptide that reduces homologous CXCR4 interactions. Mol Cancer Ther 5:2474-2483.
43. Milligan G (2003) Constitutive activity and inverse agonists of G protein-coupled receptors: A current perspective. Mol Pharmacol 64:1271-1276.
44. Kenakin T (2001) Inverse, protean, and ligand-selective agonism: Matters of receptor conformation. FASEB J 15:598-611.
45. Beider K, et al. (2009) Interaction between CXCR4 and CCL20 pathways regulates tumor growth. PLoS ONE 4:e5125.
46. De Clercq E (2009) The AMD3100 story: The path to the discovery of a stem cell mobilizer (Mozobil). Biochem Pharmacol 77:1655-1664.
47. Flomenberg N, et al. (2005) The use of AMD3100 plus G-CSF for autologous hematopoietic progenitor cell mobilization is superior to G-CSF alone. Blood 106: 1867-1874.
48. Chapman AP, et al. (1999) Therapeutic antibody fragments with prolonged in vivo half-lives. Nat Biotechnol 17:780-783.
49. Holt LJ, Herring C, Jespers LS, Woolven BP, Tomlinson IM (2003) Domain antibodies: Proteins for therapy. Trends Biotechnol 21:484-490.
50. Harmsen MM, et al. (2007) Passive immunization of guinea pigs with llama singledomain antibody fragments against foot-and-mouth disease. Vet Microbiol 120: 193-206.