CCR5 small-molecule antagonists and monoclonal antibodies exert potent synergistic antiviral effects by cobinding to the receptor

Molecular Pharmacology

Volumn 72, Issue 1, 2007, Pages 18-28

  Ji, Changhua ^a   Zhang, Jun ^a   Dioszegi, Marianna ^a   Chiu, Sophie ^b   Rao, Eileen ^a   DeRosier, Andre ^a   Cammack, Nick ^a   Brandt, Michael ^c   Sankuratri, Surya ^a  

^a Roche Palo Alto ^*  (United States)

^b Genome Informatics   (United States)

^c Pharmaceuticals Division   (Germany)

Author keywords

[No Author keywords available]

Indexed keywords

APLAVIROC; CHEMOKINE RECEPTOR CCR5 ANTAGONIST; ENFUVIRTIDE; EPITOPE; MARAVIROC; MONOCLONAL ANTIBODY; MONOCLONAL ANTIBODY 2D7; MONOCLONAL ANTIBODY 45523; MONOCLONAL ANTIBODY ROAB13; MONOCLONAL ANTIBODY ROAB14; UNCLASSIFIED DRUG; VICRIVIROC;

ANTIVIRAL ACTIVITY; ARTICLE; BINDING AFFINITY; CELL FUSION; COMPETITIVE INHIBITION; CONTROLLED STUDY; CORRELATION ANALYSIS; DRUG INHIBITION; DRUG MECHANISM; DRUG POTENTIATION; EMBRYO; HUMAN; HUMAN CELL; HUMAN IMMUNODEFICIENCY VIRUS; HUMAN IMMUNODEFICIENCY VIRUS INFECTION; PRIORITY JOURNAL;

ANIMALS; ANTI-HIV AGENTS; ANTIBODIES, MONOCLONAL; CHO CELLS; CRICETINAE; CRICETULUS; DRUG SYNERGISM; HIV ENVELOPE PROTEIN GP41; PEPTIDE FRAGMENTS; RECEPTORS, CCR5;

EID: 34347255694     PISSN: 0026895X     EISSN: 15210111     Source Type: Journal    
DOI: 10.1124/mol.107.035055     Document Type: Article

References (40)

1. Barbaro G, Scozzafava A, Mastrolorenzo A, and Supuran CT (2005) Highly active antiretroviral therapy: current state of the art, new agents and their pharmacological interactions useful for improving therapeutic outcome. Curr Pharm Des 11:1805-1843.
2. Blanpain C, Vanderwinden JM, Cihak J, Wittamer V, Le Poul E, Issafras H, Stangassinger M, Vassart G, Marullo S, Schlndorff D, et al. (2002) Multiple active states and oligomerization of CCR5 revealed by functional properties of monoclonal antibodies. Mol Biol Cell 13:723-737.
3. Bliss CI (1939) The toxicity of poisons applied jointly. Ann Appl Biol 26:585-615.
4. Chou TC (2006) Theoretical basis, experimental design, and computerized simulation of synergism and antagonism in drug combination studies. Pharmacol Rev 58:621-681.
5. Chou TC, and Talalay P (1984) Quantitative analysis of dose-effect relationships: the combined effects of multiple drugs or enzyme inhibitors. Adv Enzyme Regul 22:27-55.
6. Cruchaga C, Odriozola L, Andreola M, Tarrago-Litvak L, and Martinez-Irujo JJ (2005) Inhibition of phosphorolysis catalyzed by HIV-1 reverse transcriptase is responsible for the synergy found in combinations of 3′-azido- 3′-deoxythymidine with nonnucleoside inhibitors. Biochemistry 44:3535-3546.
7. Deng H, Liu R, Ellmeier W, Choe S, Unutmaz D, Burkhart M, Di Marzio P, Marmon S, Sutton RE, Hill CM, et al. (1996) Identification of a major co-receptor for primary isolates of HIV-1. Nature 381:661-666.
8. Dragic T, Litwin V, Allaway GP, Martin SR, Huang Y, Nagashima KA, Cayanan C, Maddon PJ, Koup RA, Moore JP, et al. (1996) HIV-1 entry into CD4+ cells is mediated by the chemokine receptor CC-CKR-5. Nature 381:667-673.
9. Dragic T, Trkola A, Thompson DA, Cormier EG, Kajumo FA, Maxwell E, Lin SW, Ying W, Smith SO, Sakmar TP, et al. (2000) A binding pocket for a small molecule inhibitor of HIV-1 entry within the transmembrane helices of CCR5. Proc Natl Acad Sci U S A 97:5639-5644.
10. Eugen-Olsen J, Iversen AK, Garred P, Koppelhus U, Pedersen C, Benfield TL, Sorensen AM, Katzenstein T, Dickmeiss E, Gerstoft J, et al. (1997) Heterozygosity for a deletion in the CKR-5 gene leads to prolonged AIDS-free survival and slower CD4 T-cell decline in a cohort of HIV-seropositive individuals. Aids 11:305-310.
11. Friedman LM, Rinon A, Schechter B, Lyass L, Lavi S, Bacus SS, Sela M, and Yarden Y (2005) Synergistic down-regulation of receptor tyrosine kinases by combinations of mAbs: implications for cancer immunotherapy. Proc Natl Acad Sci U S A 102:1915-1920.
12. Greco WR, Bravo G, and Parsons JC (1995) The search for synergy: a critical review from a response surface perspective. Pharmacol Rev 47:331-385.
13. Greco WR, Park HS, and Rustum YM (1990) Application of a new approach for the quantitation of drug synergism to the combination of cis- diamminedichloroplatinum and 1-beta-D-arabinofuranosylcytosine. Cancer Res 50:5318-5327.
14. Ji C, Brandt M, Dioszegi M, Jekle A, Schwoerer S, Challand S, Zhang J, Chen Y, Zautke L, Achhammer G, et al. (2006a) Novel CCR5 monoclonal antibodies with potent and broad-spectrum anti-HIV activities. Antiviral Res 74:125-137.
15. Ji C, Zhang J, Cammack N, and Sankuratri S (2006b) Development of a novel dual CCR5-dependent and CXCR4-dependent cell-cell fusion assay system with inducible gp160 expression. J Biomol Screen 11:65-74.
16. Laal S, Burda S, Gorny MK, Karwowska S, Buchbinder A, and Zolla-Pazner S (1994) Synergistic neutralization of human immunodeficiency virus type 1 by combinations of human monoclonal antibodies. J Virol 68:4001-4008.
17. Lazzarin A (2005) Enfuvirtide: the first HIV fusion inhibitor. Expert Opin Pharmacother 6:453-464.
18. Liu R, Paxton WA, Choe S, Ceradini D, Martin SR, Horuk R, MacDonald ME, Stuhlmann H, Koup RA, and Landau NR (1996) Homozygous defect in HIV-1 coreceptor accounts for resistance of some multiply-exposed individuals to HIV-1 infection. Cell 86:367-377.
19. Loewe S (1953) The problem of synergism and antagonism of combined drugs. Arzneimittelforschung 3:285-290.
20. Maeda K, Nakata H, Koh Y, Miyakawa T, Ogata H, Takaoka Y, Shibayama S, Sagawa K, Fukushima D, Moravek J, et al. (2004) Spirodiketopiperazine-based CCR5 inhibitor which preserves CC-chemokine/CCR5 interactions and exerts potent activity against R5 human immunodeficiency virus type 1 in vitro. J Virol 78:8654-8662.
21. Murga JD, Franti M, Pevear DC, Maddon PJ, and Olson WC (2006) Potent antiviral synergy between monoclonal antibody and small-molecule CCR5 inhibitors of human immunodeficiency virus type 1. Antimicrob Agents Chemother 50:3289-3296.
22. Nagashima KA, Thompson DA, Rosenfield SI, Maddon PJ, Dragic T, and Olson WC (2001) Human immunodeficiency virus type 1 entry inhibitors PRO 542 and T-20 are potently synergistic in blocking virus-cell and cell-cell fusion. J Infect Dis 183:1121-1125.
23. Olson WC, Rabut GE, Nagashima KA, Tran DN, Anselma DJ, Monard SP, Segal JP, Thompson DA, Kajumo F, Guo Y, et al. (1999) Differential inhibition of human immunodeficiency virus type 1 fusion, gp120 binding, and CC-chemokine activity by monoclonal antibodies to CCR5. J Virol 73:4145-4155.
24. Palani A, Shapiro S, Josien H, Bara T, Clader JW, Greenlee WJ, Cox K, Strizki JM, and Baroudy BM (2002) Synthesis, SAR, and biological evaluation of oximinopiperidino-piperidine amides. 1. Orally bioavailable CCR5 receptor antagonists with potent anti-HIV activity. J Med Chem 45:3143-3160.
25. Platt EJ, Durnin JP, and Kabat D (2005) Kinetic factors control efficiencies of cell entry, efficacies of entry inhibitors, and mechanisms of adaptation of human immunodeficiency virus. J Virol 79:4347-4356.
26. Prichard MN and Shipman C Jr. (1990) A three-dimensional model to analyze drug-drug interactions. Antiviral Res 14:181-205.
27. Safarian D, Carnec X, Tsamis F, Kajumo F, and Dragic T (2006) An anti-CCR5 monoclonal antibody and small molecule CCR5 antagonists synergize by inhibiting different stages of human immunodeficiency virus type 1 entry. Virology 352:477-484.
28. SAS Institute (1999) SAS User's Guide: Statistics, SAS Institute, Cary, NC.
29. Seibert C, Ying W, Gavrilov S, Tsamis F, Kuhmann SE, Palani A, Tagat JR, Clader JW, McCombie SW, Baroudy BM, et al. (2006) Interaction of small molecule inhibitors of HIV-1 entry with CCR5. Virology 349:41-54.
30. Strizki JM, Tremblay C, Xu S, Wojcik L, Wagner N, Gonsiorek W, Hipkin RW, Chou CC, Pugliese-Sivo C, Xiao Y, et al. (2005) Discovery and characterization of vicriviroc (SCH 417690), a CCR5 antagonist with potent activity against human immunodeficiency virus type 1. Antimicrob Agents Chemother 49:4911-4919.
31. Suhnel J (1990) Evaluation of synergism or antagonism for the combined action of antiviral agents. Antiviral Res 13:23-39.
32. Tremblay C (2004) Effects of HIV-1 entry inhibitors in combination. Curr Pharm Des 10:1861-1865.
33. Tremblay CL, Giguel F, Chou TC, Dong H, Takashima K, and Hirsch MS (2005) TAK-652, a novel CCR5 inhibitor, has favourable drug interactions with other antiretrovirals in vitro. Antivir Ther 10:967-968.
34. Trkola A, Ketas TJ, Nagashima KA, Zhao L, Cilliers T, Morris L, Moore JP, Maddon PJ, and Olson WC (2001) Potent, broad-spectrum inhibition of human immunodeficiency virus type 1 by the CCR5 monoclonal antibody PRO 140. J Virol 75:579-588.
35. Trkola A, Kuhmann SE, Strizki JM, Maxwell E, Ketas T, Morgan T, Pugach P, Xu S, Wojcik L, Tagat J, et al. (2002) HIV-1 escape from a small molecule, CCR5-specific entry inhibitor does not involve CXCR4 use. Proc Natl Acad Sci U S A 99:395-400.
36. Vijh-Warrier S, Pinter A, Honnen WJ, and Tilley SA (1996) Synergistic neutralization of human immunodeficiency virus type 1 by a chimpanzee monoclonal antibody against the V2 domain of gp120 in combination with monoclonal antibodies against the V3 loop and the CD4-binding site. J Virol 70:4466-4473.
37. Watson C, Jenkinson S, Kazmierski W, and Kenakin T (2005) The CCR5 receptor-based mechanism of action of 873140, a potent allosteric noncompetitive HIV entry inhibitor. Mol Pharmacol 67:1268-1282.
38. Wood A, and Armour D (2005) The discovery of the CCR5 receptor antagonist, UK-427,857, a new agent for the treatment of HIV infection and AIDS. Prog Med Chem 43:239-271.
39. Zhang J, Rao E, Dioszegi M, Kondru R, Derosier A, Chan E, Schwoerer S, Cammack N, Brandt M, Sankuratri S and Ji C (2007) The second extracellular loop of CCR5 contains the dominant epitopes for highly potent Anti-HIV monoclonal antibodies. Antimicrob Agents Chemother 51:1386-1397.
40. Zwick MB, Jensen R, Church S, Wang M, Stiegler G, Kunert R, Katinger H, and Burton DR (2005) Anti-human immunodeficiency virus type 1 (HIV-1) antibodies 2F5 and 4E10 require surprisingly few crucial residues in the membrane-proximal external region of glycoprotein gp41 to neutralize HIV-1. J Virol 79:1252-1261.