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Inhibition of plasma kallikrein by a highly specific active site blocking antibody.

Kenniston JA, Faucette RR, Martik D, Comeau SR, Lindberg AP, Kopacz KJ, Conley GP, Chen J, Viswanathan M, Kastrapeli N, Cosic J, Mason S, DiLeo M, Abendroth J, Kuzmic P, Ladner RC, Edwards TE, TenHoor C, Adelman BA, Nixon AE, Sexton DJ
J Biol Chem 289 23596-608 (2014)
Related entries: 4ogx, 4ogy

Cited: 69 times
EuropePMC logo PMID: 24970892

Abstract

Plasma kallikrein (pKal) proteolytically cleaves high molecular weight kininogen to generate the potent vasodilator and the pro-inflammatory peptide, bradykinin. pKal activity is tightly regulated in healthy individuals by the serpin C1-inhibitor, but individuals with hereditary angioedema (HAE) are deficient in C1-inhibitor and consequently exhibit excessive bradykinin generation that in turn causes debilitating and potentially fatal swelling attacks. To develop a potential therapeutic agent for HAE and other pKal-mediated disorders, we used phage display to discover a fully human IgG1 monoclonal antibody (DX-2930) against pKal. In vitro experiments demonstrated that DX-2930 potently inhibits active pKal (Ki = 0.120 ± 0.005 nM) but does not target either the zymogen (prekallikrein) or any other serine protease tested. These findings are supported by a 2.1-Å resolution crystal structure of pKal complexed to a DX-2930 Fab construct, which establishes that the pKal active site is fully occluded by the antibody. DX-2930 injected subcutaneously into cynomolgus monkeys exhibited a long half-life (t½ ∼ 12.5 days) and blocked high molecular weight kininogen proteolysis in activated plasma in a dose- and time-dependent manner. Furthermore, subcutaneous DX-2930 reduced carrageenan-induced paw edema in rats. A potent and long acting inhibitor of pKal activity could be an effective treatment option for pKal-mediated diseases, such as HAE.

Articles - 4pub mentioned but not cited (2)

  1. Inhibition of plasma kallikrein by a highly specific active site blocking antibody. Kenniston JA, Faucette RR, Martik D, Comeau SR, Lindberg AP, Kopacz KJ, Conley GP, Chen J, Viswanathan M, Kastrapeli N, Cosic J, Mason S, DiLeo M, Abendroth J, Kuzmic P, Ladner RC, Edwards TE, TenHoor C, Adelman BA, Nixon AE, Sexton DJ. J Biol Chem 289 23596-23608 (2014)
  2. Structural insights into antigen recognition of an anti-β-(1,6)-β-(1,3)-D-glucan antibody. Sung KH, Josewski J, Dübel S, Blankenfeldt W, Rau U. Sci Rep 8 13652 (2018)


Reviews citing this publication (23)

  1. Phage display-derived human antibodies in clinical development and therapy. Frenzel A, Schirrmann T, Hust M. MAbs 8 1177-1194 (2016)
  2. Phage Display Derived Monoclonal Antibodies: From Bench to Bedside. Alfaleh MA, Alsaab HO, Mahmoud AB, Alkayyal AA, Jones ML, Mahler SM, Hashem AM. Front Immunol 11 1986 (2020)
  3. Advances in phage display technology for drug discovery. Omidfar K, Daneshpour M. Expert Opin Drug Discov 10 651-669 (2015)
  4. Kallikreins - The melting pot of activity and function. Kalinska M, Meyer-Hoffert U, Kantyka T, Potempa J. Biochimie 122 270-282 (2016)
  5. Hereditary angioedema: the plasma contact system out of control. De Maat S, Hofman ZLM, Maas C. J Thromb Haemost 16 1674-1685 (2018)
  6. Plasma contact factors as therapeutic targets. Tillman BF, Gruber A, McCarty OJT, Gailani D. Blood Rev 32 433-448 (2018)
  7. Plant/Bacterial Virus-Based Drug Discovery, Drug Delivery, and Therapeutics. Sokullu E, Soleymani Abyaneh H, Gauthier MA. Pharmaceutics 11 E211 (2019)
  8. Phage Display Technology as a Powerful Platform for Antibody Drug Discovery. Nagano K, Tsutsumi Y. Viruses 13 178 (2021)
  9. Science for surgeons: understanding pump thrombogenesis in continuous-flow left ventricular assist devices. de Biasi AR, Manning KB, Salemi A. J Thorac Cardiovasc Surg 149 667-673 (2015)
  10. Breakthroughs in hereditary angioedema management: a systematic review of approved drugs and those under research. Nicola S, Rolla G, Brussino L. Drugs Context 8 212605 (2019)
  11. Proteolytic activity of contact factor zymogens. Shamanaev A, Emsley J, Gailani D. J Thromb Haemost 19 330-341 (2021)
  12. Lanadelumab for the Prophylactic Treatment of Hereditary Angioedema with C1 Inhibitor Deficiency: A Review of Preclinical and Phase I Studies. Busse PJ, Farkas H, Banerji A, Lumry WR, Longhurst HJ, Sexton DJ, Riedl MA. BioDrugs 33 33-43 (2019)
  13. Quality of life in patients with allergic and immunologic skin diseases: in the eye of the beholder. Di Agosta E, Salvati L, Corazza M, Baiardini I, Ambrogio F, Angileri L, Antonelli E, Belluzzo F, Bonamonte D, Bonzano L, Brancaccio R, Custurone P, De Marco A, Detoraki A, Di Guida A, Di Leo E, Fantò M, Fassio F, Ferrucci SM, Foti C, Gallo R, Gatta A, Guarneri F, Guidolin L, Hansel K, Lamacchia D, Lombardo C, Minciullo PL, Napolitano M, Pannofino A, Paravisi A, Parente R, Passante M, Patruno C, Peroni D, Quecchia C, Schettini N, Spadaro G, Stingeni L, Tarrini D, Tramontana M, Nettis E, Rossi O. Clin Mol Allergy 19 26 (2021)
  14. A comprehensive review on current understanding of bradykinin in COVID-19 and inflammatory diseases. Rex DAB, Vaid N, Deepak K, Dagamajalu S, Prasad TSK. Mol Biol Rep 49 9915-9927 (2022)
  15. Icatibant for the treatment of hereditary angioedema with C1-inhibitor deficiency in adolescents and in children aged over 2 years. Farkas H, Kőhalmi KV. Expert Rev Clin Immunol 14 447-460 (2018)
  16. Antibody Libraries as Tools to Discover Functional Antibodies and Receptor Pleiotropism. Lin CW, Lerner RA. Int J Mol Sci 22 4123 (2021)
  17. Pharmacological Management of Hereditary Angioedema with C1-Inhibitor Deficiency in Pediatric Patients. Farkas H. Paediatr Drugs 20 135-151 (2018)
  18. Investigational drugs in phase I and phase II clinical trials for hereditary angioedema. Farkas H, Debreczeni ML, Kőhalmi KV. Expert Opin Investig Drugs 27 87-103 (2018)
  19. Lanadelumab Injection Treatment For The Prevention Of Hereditary Angioedema (HAE): Design, Development And Place In Therapy. Bova M, Valerieva A, Wu MA, Senter R, Perego F. Drug Des Devel Ther 13 3635-3646 (2019)
  20. Lanadelumab: A Review in Hereditary Angioedema. Syed YY. Drugs 79 1777-1784 (2019)
  21. Application of recombinant antibodies for treatment of Clostridioides difficile infection: Current status and future perspective. Raeisi H, Azimirad M, Nabavi-Rad A, Asadzadeh Aghdaei H, Yadegar A, Zali MR. Front Immunol 13 972930 (2022)
  22. Interventions for the long-term prevention of hereditary angioedema attacks. Beard N, Frese M, Smertina E, Mere P, Katelaris C, Mills K. Cochrane Database Syst Rev 11 CD013403 (2022)
  23. Human plasma kallikrein: roles in coagulation, fibrinolysis, inflammation pathways, and beyond. Motta G, Juliano L, Chagas JR. Front Physiol 14 1188816 (2023)

Articles citing this publication (44)

  1. Inhibiting Plasma Kallikrein for Hereditary Angioedema Prophylaxis. Banerji A, Busse P, Shennak M, Lumry W, Davis-Lorton M, Wedner HJ, Jacobs J, Baker J, Bernstein JA, Lockey R, Li HH, Craig T, Cicardi M, Riedl M, Al-Ghazawi A, Soo C, Iarrobino R, Sexton DJ, TenHoor C, Kenniston JA, Faucette R, Still JG, Kushner H, Mensah R, Stevens C, Biedenkapp JC, Chyung Y, Adelman B. N Engl J Med 376 717-728 (2017)
  2. Effect of Lanadelumab Compared With Placebo on Prevention of Hereditary Angioedema Attacks: A Randomized Clinical Trial. Banerji A, Riedl MA, Bernstein JA, Cicardi M, Longhurst HJ, Zuraw BL, Busse PJ, Anderson J, Magerl M, Martinez-Saguer I, Davis-Lorton M, Zanichelli A, Li HH, Craig T, Jacobs J, Johnston DT, Shapiro R, Yang WH, Lumry WR, Manning ME, Schwartz LB, Shennak M, Soteres D, Zaragoza-Urdaz RH, Gierer S, Smith AM, Tachdjian R, Wedner HJ, Hebert J, Rehman SM, Staubach P, Schranz J, Baptista J, Nothaft W, Maurer M, HELP Investigators. JAMA 320 2108-2121 (2018)
  3. Proteolytic properties of single-chain factor XII: a mechanism for triggering contact activation. Ivanov I, Matafonov A, Sun MF, Cheng Q, Dickeson SK, Verhamme IM, Emsley J, Gailani D. Blood 129 1527-1537 (2017)
  4. A comparison of the effects of factor XII deficiency and prekallikrein deficiency on thrombus formation. Kokoye Y, Ivanov I, Cheng Q, Matafonov A, Dickeson SK, Mason S, Sexton DJ, Renné T, McCrae K, Feener EP, Gailani D. Thromb Res 140 118-124 (2016)
  5. Factor XI Deficiency Alters the Cytokine Response and Activation of Contact Proteases during Polymicrobial Sepsis in Mice. Bane CE, Ivanov I, Matafonov A, Boyd KL, Cheng Q, Sherwood ER, Tucker EI, Smiley ST, McCarty OJ, Gruber A, Gailani D. PLoS One 11 e0152968 (2016)
  6. A mechanism for hereditary angioedema with normal C1 inhibitor: an inhibitory regulatory role for the factor XII heavy chain. Ivanov I, Matafonov A, Sun MF, Mohammed BM, Cheng Q, Dickeson SK, Kundu S, Verhamme IM, Gruber A, McCrae K, Gailani D. Blood 133 1152-1163 (2019)
  7. A Camelid-derived Antibody Fragment Targeting the Active Site of a Serine Protease Balances between Inhibitor and Substrate Behavior. Kromann-Hansen T, Oldenburg E, Yung KW, Ghassabeh GH, Muyldermans S, Declerck PJ, Huang M, Andreasen PA, Ngo JC. J Biol Chem 291 15156-15168 (2016)
  8. An open-label study to evaluate the long-term safety and efficacy of lanadelumab for prevention of attacks in hereditary angioedema: design of the HELP study extension. Riedl MA, Bernstein JA, Craig T, Banerji A, Magerl M, Cicardi M, Longhurst HJ, Shennak MM, Yang WH, Schranz J, Baptista J, Busse PJ. Clin Transl Allergy 7 36 (2017)
  9. Lanadelumab demonstrates rapid and sustained prevention of hereditary angioedema attacks. Riedl MA, Maurer M, Bernstein JA, Banerji A, Longhurst HJ, Li HH, Lu P, Hao J, Juethner S, Lumry WR, HELP Investigators. Allergy 75 2879-2887 (2020)
  10. Functional selection of protease inhibitory antibodies. Lopez T, Mustafa Z, Chen C, Lee KB, Ramirez A, Benitez C, Luo X, Ji RR, Ge X. Proc Natl Acad Sci U S A 116 16314-16319 (2019)
  11. Plasma kallikrein structure reveals apple domain disc rotated conformation compared to factor XI. Li C, Voos KM, Pathak M, Hall G, McCrae KR, Dreveny I, Li R, Emsley J. J Thromb Haemost 17 759-770 (2019)
  12. A kallikrein-targeting RNA aptamer inhibits the intrinsic pathway of coagulation and reduces bradykinin release. Steen Burrell KA, Layzer J, Sullenger BA. J Thromb Haemost 15 1807-1817 (2017)
  13. Design and characterization of α1-antitrypsin variants for treatment of contact system-driven thromboinflammation. de Maat S, Sanrattana W, Mailer RK, Parr NMJ, Hessing M, Koetsier RM, Meijers JCM, Pasterkamp G, Renné T, Maas C. Blood 134 1658-1669 (2019)
  14. Impact of lanadelumab on health-related quality of life in patients with hereditary angioedema in the HELP study. Lumry WR, Weller K, Magerl M, Banerji A, Longhurst HJ, Riedl MA, Lewis HB, Lu P, Devercelli G, Jain G, Maurer M, HELP Study Investigators. Allergy 76 1188-1198 (2021)
  15. Long-term prevention of hereditary angioedema attacks with lanadelumab: The HELP OLE Study. Banerji A, Bernstein JA, Johnston DT, Lumry WR, Magerl M, Maurer M, Martinez-Saguer I, Zanichelli A, Hao J, Inhaber N, Yu M, Riedl MA, HELP OLE Investigators. Allergy 77 979-990 (2022)
  16. The Plasma Kallikrein-Kininogen Pathway Is Critical in the Pathogenesis of Colitis in Mice. Wang B, Yang A, Zhao Z, He C, Liu Y, Colman RW, Dai J, Wu Y. Front Immunol 9 21 (2018)
  17. Comparing Pathways of Bradykinin Formation in Whole Blood From Healthy Volunteers and Patients With Hereditary Angioedema Due to C1 Inhibitor Deficiency. Charest-Morin X, Hébert J, Rivard GÉ, Bonnefoy A, Wagner E, Marceau F. Front Immunol 9 2183 (2018)
  18. Psychology and hereditary angioedema: A systematic review. Savarese L, Mormile I, Bova M, Petraroli A, Maiello A, Spadaro G, Freda MF. Allergy Asthma Proc 42 e1-e7 (2021)
  19. 2D-LC-MS/MS to measure cleaved high-molecular-weight kininogen in human plasma as a biomarker for C1-INH-HAE. Zhang G, Sexton DJ, Faucette RR, Qiu Y, Wu J. Bioanalysis 9 1477-1491 (2017)
  20. Design of Specific Serine Protease Inhibitors Based on a Versatile Peptide Scaffold: Conversion of a Urokinase Inhibitor to a Plasma Kallikrein Inhibitor. Xu P, Xu M, Jiang L, Yang Q, Luo Z, Dauter Z, Huang M, Andreasen PA. J Med Chem 58 8868-8876 (2015)
  21. Measurement of Bradykinin Formation and Degradation in Blood Plasma: Relevance for Acquired Angioedema Associated With Angiotensin Converting Enzyme Inhibition and for Hereditary Angioedema Due to Factor XII or Plasminogen Gene Variants. Marceau F, Rivard GE, Gauthier JM, Binkley KE, Bonnefoy A, Boccon-Gibod I, Bouillet L, Picard M, Levesque G, Elfassy HL, Bachelard H, Hébert J, Bork K. Front Med (Lausanne) 7 358 (2020)
  22. Protease activity in single-chain prekallikrein. Ivanov I, Verhamme IM, Sun MF, Mohammed B, Cheng Q, Matafonov A, Dickeson SK, Joseph K, Kaplan AP, Gailani D. Blood 135 558-567 (2020)
  23. An algebraic model for the kinetics of covalent enzyme inhibition at low substrate concentrations. Kuzmič P, Solowiej J, Murray BW. Anal Biochem 484 82-90 (2015)
  24. Increased fibrinolysis-induced bradykinin formation in hereditary angioedema confirmed using stored plasma and biotechnological inhibitors. Marceau F, Bachelard H, Rivard GÉ, Hébert J. BMC Res Notes 12 291 (2019)
  25. A modular map of Bradykinin-mediated inflammatory signaling network. Rex DAB, Deepak K, Vaid N, Dagamajalu S, Kandasamy RK, Flo TH, Keshava Prasad TS. J Cell Commun Signal 16 301-310 (2022)
  26. A protein scaffold, engineered SPINK2, for generation of inhibitors with high affinity and specificity against target proteases. Nishimiya D, Kawaguchi Y, Kodama S, Nasu H, Yano H, Yamaguchi A, Tamura M, Hashimoto R. Sci Rep 9 11436 (2019)
  27. Activity of Factor XII-Locarno. Mohammed BM, Ivanov I, Matafonov A, Emsley J, Gailani D. Res Pract Thromb Haemost 2 168-173 (2018)
  28. Protease Inhibition Mechanism of Camelid-like Synthetic Human Antibodies. Nam DH, Lee KB, Kruchowy E, Pham H, Ge X. Biochemistry 59 3802-3812 (2020)
  29. Simple Approach to Accurately Predict Pharmacokinetics of Therapeutic Monoclonal Antibodies after Subcutaneous Injection in Humans. Haraya K, Tachibana T. Clin Pharmacokinet 60 111-120 (2021)
  30. Structural Basis for Activity and Specificity of an Anticoagulant Anti-FXIa Monoclonal Antibody and a Reversal Agent. Ely LK, Lolicato M, David T, Lowe K, Kim YC, Samuel D, Bessette P, Garcia JL, Mikita T, Minor DL, Coughlin SR. Structure 26 187-198.e4 (2018)
  31. Letter Effectiveness of lanadelumab for preventing hereditary angioedema attacks: Subgroup analyses from the HELP study. Johnston DT, Busse PJ, Riedl MA, Maurer M, Anderson J, Nurse C, Inhaber N, Yu M, Banerji A, HELP Study Investigators. Clin Exp Allergy 51 1391-1395 (2021)
  32. Bradykinin 1 Receptor Antagonist BI1026706 Does Not Reduce Central Retinal Thickness in Center-Involved Diabetic Macular Edema. Lang GE, Tadayoni R, Tang W, Barth C, Weiss-Haljiti C, Chong V, BI 1026706 Study Group. Transl Vis Sci Technol 9 25 (2020)
  33. C1 inhibitor and prolylcarboxypeptidase modulate prekallikrein activation on endothelial cells. Merkulova AA, Abdalian S, Silbak S, Pinheiro A, Schmaier AH. J Allergy Clin Immunol 152 961-971.e7 (2023)
  34. Generation of highly selective monoclonal antibodies inhibiting a recalcitrant protease using decoy designs. Lee KB, Dunn ZS, Lopez T, Mustafa Z, Ge X. Biotechnol Bioeng 117 3664-3676 (2020)
  35. Indirect Comparison of Lanadelumab and Intravenous C1-INH Using Data from the HELP and CHANGE Studies: Bayesian and Frequentist Analyses. Mendivil J, Malmenäs M, Haeussler K, Hunger M, Jain G, Devercelli G. Drugs R D 21 113-121 (2021)
  36. Network meta-analysis for indirect comparison of lanadelumab and berotralstat for the treatment of hereditary angioedema. Watt M, Malmenäs M, Romanus D, Haeussler K. J Comp Eff Res 12 e220188 (2023)
  37. Pharmacokinetics, Pharmacodynamics, and Exposure-Response of Lanadelumab for Hereditary Angioedema. Wang Y, Marier JF, Kassir N, Chang C, Martin P. Clin Transl Sci 13 1208-1216 (2020)
  38. Substrate derived sequences act as subsite-blocking motifs in protease inhibitory antibodies. Choe H, Antee T, Ge X. Protein Sci 32 e4691 (2023)
  39. Therapeutic management of hereditary angioedema: past, present, and future. Valerieva A, Nedeva D, Yordanova V, Petkova E, Staevska M. Balkan Med J 38 89-103 (2021)
  40. Titanium is a potent inducer of contact activation: implications for intravascular devices. Litvak M, Shamanaev A, Zalawadiya S, Matafonov A, Kobrin A, Feener EP, Wallisch M, Tucker EI, McCarty OJT, Gailani D. J Thromb Haemost 21 1200-1213 (2023)
  41. Effectiveness and safety of lanadelumab in ethnic and racial minority subgroups of patients with hereditary angioedema: results from phase 3 studies. Craig TJ, Zaragoza-Urdaz RH, Li HH, Yu M, Ren H, Juethner S, Anderson J, HELP and HELP OLE Study Investigators. Allergy Asthma Clin Immunol 18 85 (2022)
  42. Case Reports Hereditary Angioedema. Banerjee A, Bermudez N, Gould MB, Ramlatchan SR, Ganti L. Cureus 15 e42088 (2023)
  43. Oral FXIIa inhibitor KV998086 suppresses FXIIa and single chain FXII mediated kallikrein kinin system activation. Clermont AC, Murugesan N, Edwards HJ, Lee DK, Bayliss NP, Duckworth EJ, Pethen SJ, Hampton SL, Gailani D, Feener EP. Front Pharmacol 14 1287487 (2023)
  44. Structural Considerations in Affinity Maturation of Antibody-Based Biotherapeutic Candidates. Comeau SR, Thorsteinson N, Kumar S. Methods Mol Biol 2552 309-321 (2023)


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