i-bodies, Human Single Domain Antibodies That Antagonize Chemokine Receptor CXCR4

被引:47
|
作者
Griffiths, Katherine [1 ]
Dolezal, Olan [2 ]
Cao, Benjamin [3 ,4 ]
Nilsson, Susan K. [3 ,4 ]
See, Heng B. [5 ,6 ]
Pfleger, Kevin D. G. [5 ,6 ,7 ]
Roche, Michael [8 ,9 ]
Gorry, Paul R. [10 ]
Pow, Andrew [1 ,13 ]
Viduka, Katerina [1 ,14 ]
Lim, Kevin [1 ,15 ]
Lu, Bernadine G. C. [1 ,16 ]
Chang, Denison H. C. [1 ,17 ]
Murray-Rust, Thomas [1 ]
Kvansakul, Marc [11 ]
Perugini, Matthew A. [11 ]
Dogovski, Con [11 ,18 ]
Doerflinger, Marcel [1 ,19 ]
Zhang, Yuan [12 ]
Parisi, Kathy [1 ,11 ]
Casey, Joanne L. [1 ,19 ]
Nuttall, Stewart D. [2 ]
Foley, Michael [1 ,11 ]
机构
[1] AdAlta Pty Ltd, 15-2 Pk Dr, Bundoora, Vic 3083, Australia
[2] CSIRO Mfg, Biomed Mfg, 343 Royal Parade, Parkville, Vic 3052, Australia
[3] Monash Univ, Australian Regenerat Med Inst, Wellington Rd, Clayton, Vic 3800, Australia
[4] CSIRO Mfg, Biomed Mfg, Bayview Ave, Clayton, Vic 3168, Australia
[5] Harry Perkins Inst Med Res, Nedlands, WA 6009, Australia
[6] Univ Western Australia, Ctr Med Res, Crawley, WA 6009, Australia
[7] Dimerix Biosci Ltd, Nedlands, WA 6009, Australia
[8] Univ Melbourne, Doherty Inst Infect & Immun, 792 Elizabeth St, Melbourne, Vic 3000, Australia
[9] Burnet Inst, 85 Commercial Rd, Melbourne, Vic 3004, Australia
[10] RMIT Univ, Coll Sci Engn & Hlth, Sch Hlth & Biomed Sci, Melbourne, Vic 3001, Australia
[11] La Trobe Univ, La Trobe Inst Mol Sci, Dept Biochem & Genet, Melbourne, Vic 3086, Australia
[12] Univ Melbourne, St Vincents Hosp, Dept Med, Fitzroy, Vic 3065, Australia
[13] Compugen Ltd, 260 East Grand Ave, San Francisco, CA 94080 USA
[14] AgriBio Ctr, Dept Econ Dev Jobs Transport & Resources, 5 Ring Rd, Bundoora, Vic 3083, Australia
[15] Imunexus, 343 Royal Parade, Parkville, Vic 3052, Australia
[16] CSL Ltd, 45 Poplar Rd, Parkville, Vic 3052, Australia
[17] Virbac, Milperra, NSW 2214, Australia
[18] Univ Melbourne, Dept Biochem & Mol Biol, Mol Sci & Biotechnol Inst Bio21, Melbourne, Vic 3010, Australia
[19] Nexvet, 21-31 Wright St, Clayton, Vic 3168, Australia
关键词
HUMAN-IMMUNODEFICIENCY-VIRUS; HEMATOPOIETIC STEM; MONOCLONAL-ANTIBODIES; RAPID MOBILIZATION; CRYSTAL-STRUCTURE; ANTIGEN RECEPTOR; PROGENITOR CELLS; AMD3100; HIV-1; FRAGMENTS;
D O I
10.1074/jbc.M116.721050
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
CXCR4 is a G protein-coupled receptor with excellent potential as a therapeutic target for a range of clinical conditions, including stem cell mobilization, cancer prognosis and treatment, fibrosis therapy, and HIV infection. We report here the development of a fully human single-domain antibody-like scaffold termed an "i-body," the engineering of which produces an i-body library possessing a long complementarity determining region binding loop, and the isolation and characterization of a panel of i-bodies with activity against human CXCR4. The CXCR4-specific i-bodies show antagonistic activity in a range of in vitro and in vivo assays, including inhibition of HIV infection, cell migration, and leukocyte recruitment but, importantly, not the mobilization of hematopoietic stem cells. Epitope mapping of the three CXCR4 i-bodies AM3-114, AM4-272, and AM3-523 revealed binding deep in the binding pocket of the receptor.
引用
收藏
页码:12641 / 12657
页数:17
相关论文
共 50 条
  • [1] Imaging agents for the chemokine receptor 4 (CXCR4)
    Kuil, Joeri
    Buckle, Tessa
    van Leeuwen, Fijs W. B.
    CHEMICAL SOCIETY REVIEWS, 2012, 41 (15) : 5239 - 5261
  • [2] Solubilization of the chemokine receptor CXCR4
    Staudinger, R
    Bandres, JC
    BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 2000, 274 (01) : 153 - 156
  • [3] Soluble chemokine receptor CXCR4 is present in human sera
    Malvoisin, Etienne
    Livrozet, Jean-Michel
    Makloufi, Djamila
    Vincent, Nadine
    ANALYTICAL BIOCHEMISTRY, 2011, 414 (02) : 202 - 207
  • [4] CXCR4 chemokine receptor antagonists: perspectives in SCLC
    Burger, Jan A.
    Stewart, David J.
    EXPERT OPINION ON INVESTIGATIONAL DRUGS, 2009, 18 (04) : 481 - 490
  • [5] Inhibition of the human chemokine receptor CXCR4 by antisense phosphorothioate oligodeoxyribonucleotides
    Kusunoki, A
    Saitou, T
    Miyano-Kurosaki, N
    Takaku, H
    FEBS LETTERS, 2001, 488 (1-2) : 64 - 68
  • [6] Antibodies Targeting Chemokine Receptors CXCR4 and ACKR3
    Bobkov, Vladimir
    Arimont, Marta
    Zarca, Aurelien
    De Groof, Timo W. M.
    van der Woning, Bas
    de Haard, Hans
    Smit, Martine J.
    MOLECULAR PHARMACOLOGY, 2019, 96 (06) : 753 - 764
  • [7] Crystal structure of the chemokine receptor CXCR4 in complex with a viral chemokine
    Qin, Ling
    Kufareva, Irina
    Holden, Lauren G.
    Wang, Chong
    Zheng, Yi
    Zhao, Chunxia
    Fenalti, Gustavo
    Wu, Huixian
    Han, Gye Won
    Cherezov, Vadim
    Abagyan, Ruben
    Stevens, Raymond C.
    Handel, Tracy M.
    SCIENCE, 2015, 347 (6226) : 1117 - 1122
  • [8] Kinetic Analysis of the Early Signaling Steps of the Human Chemokine Receptor CXCR4
    Perpina-Viciano, Cristina
    Isbilir, Ali
    Zarca, Aurelien
    Caspar, Birgit
    Kilpatrick, Laura E.
    Hill, Stephen J.
    Smit, Martine J.
    Lohse, Martin J.
    Hoffmann, Carsten
    MOLECULAR PHARMACOLOGY, 2020, 98 (02) : 72 - 87
  • [9] Structure-Based Development of Antagonists for Chemokine Receptor CXCR4
    Zhang, Chongqian
    Hou, Tingjun
    Feng, Zhiwei
    Li, Youyong
    CURRENT COMPUTER-AIDED DRUG DESIGN, 2013, 9 (01) : 60 - 75
  • [10] CXC chemokine receptor 4 (CXCR4) blockade in cancer treatment
    Bao, Shunshun
    Darvishi, Mohammad
    Amin, Ali
    Al-Haideri, Maysoon T.
    Patra, Indrajit
    Kashikova, Khadisha
    Ahmad, Irfan
    Alsaikhan, Fahad
    Al-qaim, Zahraa Haleem
    Al-Gazally, Moaed E.
    Kiasari, Bahman Abedi
    Tavakoli-Far, Bahareh
    Sidikov, Akmal A.
    Mustafa, Yasser Fakri
    Akhavan-Sigari, Reza
    JOURNAL OF CANCER RESEARCH AND CLINICAL ONCOLOGY, 2023, 149 (10) : 7945 - 7968