Anti-neuropilin-1 (MNRP1685A): Unexpected pharmacokinetic differences across species, from preclinical models to humans

Pharmaceutical Research

Volumn 29, Issue 9, 2012, Pages 2512-2521

  Xin, Yan ^a   Bai, Shuang ^a   Damico Beyer, Lisa A ^a   Jin, Denise ^a   Liang, Wei Ching ^a   Wu, Yan ^a   Theil, Frank Peter ^a   Joshi, Amita ^a   Lu, Yanmei ^a   Lowe, John ^a   Maia, Mauricio ^a   Brachmann, Rainer K ^a   Xiang, Hong ^a  

^a GENENTECH INC   (United States)

Author keywords

Angiogenesis; MNRP1685A; Neuropilin 1; Nonlinear PK

Indexed keywords

ANTINEOPLASTIC AGENT; HUMAN MONOCLONAL ANTIBODY; MNRP 1685A; NEUROPILIN 1; UNCLASSIFIED DRUG;

ADVANCED CANCER; ANIMAL CELL; ANIMAL EXPERIMENT; ANTINEOPLASTIC ACTIVITY; ARTICLE; CANCER PATIENT; CLINICAL ARTICLE; CONTROLLED STUDY; DRUG CLEARANCE; DRUG DESIGN; DRUG DOSE COMPARISON; DRUG DOSE REGIMEN; DRUG RECEPTOR BINDING; DRUG SCREENING; DRUG TARGETING; FEMALE; HAPLORHINI; HUMAN; HUMAN VERSUS ANIMAL COMPARISON; IN VIVO STUDY; MALE; MOUSE; NONHUMAN; PRIORITY JOURNAL; PROTEIN EXPRESSION; RAT; RECEPTOR AFFINITY; SINGLE DRUG DOSE; SOLID TUMOR; SPECIES DIFFERENCE;

ANIMALS; ANTIBODIES, MONOCLONAL; HUMANS; MODELS, BIOLOGICAL; NEUROPILIN-1; SPECIES SPECIFICITY;

EID: 84866736720     PISSN: 07248741     EISSN: 1573904X     Source Type: Journal    
DOI: 10.1007/s11095-012-0781-x     Document Type: Article

References (36)

1. Dirksand NL, Meibohm B. Population pharmacokinetics of therapeutic monoclonal antibodies. Clin Pharmacokinet. 2010;49:633-59.
2. Lobo ED, Hansen RJ, Balthasar JP. Antibody pharmacokinetics and pharmacodynamics. J Pharm Sci. 2004;93:2645-68.
3. Mager DE. Target-mediated drug disposition and dynamics. Biochem Pharmacol. 2006;72:1-10.
4. Roskos LK, Davis CG, Schwab GM. The clinical pharmacology of therapeutic monoclonal antibodies. Drug Dev Res. 2004;61:108-20.
5. Tabrizi MA, Tseng CM, Roskos LK. Elimination mechanisms of therapeutic monoclonal antibodies. Drug Discov Today. 2006;11:81-8.
6. Deng R, Iyer S, Theil FP, Mortensen DL, Fielder PJ, Prabhu S. Projecting human pharmacokinetics of therapeutic antibodies from nonclinical data: What have we learned? MAbs. 2010;3:61-6.
7. Ling J, Zhou H, Jiao Q, Davis HM. Interspecies scaling of therapeutic monoclonal antibodies: Initial look. J Clin Pharmacol. 2009;49:1382-402.
8. Vugmeyster Y, Szklut P, Wensel D, Ross J, Xu X, AwwadM,Gill D, Tchistiakov L, Warner G. Complex pharmacokinetics of a humanized antibody against human amyloid Beta Peptide, anti-abeta ab2, in nonclinical species. Pharm Res. 2011;28:1696-706.
9. Bumbaca D, Wong A, Drake E, Reyes AE, 2nd, Lin BC, Stephan JP, Desnoyers L, Shen BQ, Dennis MS. Highly specific off-target binding identified and eliminated during the humanization of an antibody against FGF receptor 4. MAbs 2011;3:376-86..
10. Vugmeyster Y, Guay H, Szklut P, Qian MD, Jin M, Widom A, Spaulding V, Bennett F, Lowe L, Andreyeva T, Lowe D, Lane S, Thom G, Valge-Archer V, Gill D, Young D, Bloom L. In vitro potency, pharmacokinetic profiles, and pharmacological activity of optimized anti-IL-21R antibodies in a mouse model of lupus. MAbs. 2010;2:335-46.
11. Bielenberg DR, Pettaway CA, Takashima S, Klagsbrun M. Neuropilins in neoplasms: Expression, regulation, and function. Exp Cell Res. 2006;312:584-93.
12. Heand Z, Tessier-Lavigne M. Neuropilin is a receptor for the axonal chemorepellent Semaphorin III. Cell. 1997;90:739-51.
13. Kawasaki T, Kitsukawa T, Bekku Y, Matsuda Y, Sanbo M, Yagi T, Fujisawa H. A requirement for neuropilin-1 in embryonic vessel formation. Development. 1999;126:4895-902.
14. Soker S, Takashima S, Miao HQ, Neufeld G, Klagsbrun M. Neuropilin-1 is expressed by endothelial and tumor cells as an isoform-specific receptor for vascular endothelial growth factor. Cell. 1998;92:735-45.
15. Bernatchez PN, Rollin S, Soker S, Sirois MG. Relative effects of VEGF-A and VEGF-C on endothelial cell proliferation, migration and PAF synthesis: Role of neuropilin-1. J Cell Biochem. 2002;85:629-39.
16. Chen H, He Z, Bagri A, Tessier-Lavigne M. Semaphorinneuropilin interactions underlying sympathetic axon responses to class III semaphorins. Neuron. 1998;21:1283-90.
17. Fujisawa H. From the discovery of neuropilin to the determination of its adhesion sites. Adv Exp Med Biol. 2002;515:1-12.
18. Mamluk R, Gechtman Z, Kutcher ME, Gasiunas N, Gallagher J, Klagsbrun M. Neuropilin-1 binds vascular endothelial growth factor 165, placenta growth factor-2, and heparin via its b1b2 domain. J Biol Chem. 2002;277:24818-25.
19. Cackowski FC, Xu L, Hu B, Cheng SY. Identification of two novel alternatively spliced Neuropilin-1 isoforms. Genomics. 2004; 84:82-94.
20. Rossignol M, Gagnon ML, Klagsbrun M. Genomic organization of human neuropilin-1 and neuropilin-2 genes: Identification and distribution of splice variants and soluble isoforms. Genomics. 2000;70:211-22.
21. Gagnon ML, Bielenberg DR, Gechtman Z, Miao HQ, Takashima S, Soker S, Klagsbrun M. Identification of a natural soluble neuropilin-1 that binds vascular endothelial growth factor: In vivo expression and antitumor activity. Proc Natl Acad Sci U S A. 2000;97:2573-8.
22. Lu Y, Xiang H, Liu P, Tong RR, Watts RJ, Koch AW, Sandoval WN, Damico LA, Wong WL, Meng YG. Identification of circulating neuropilin-1 and dose-dependent elevation following antineuropilin-1 antibody administration. MAbs. 2009;1:364-9.
23. Pan Q, Chathery Y, Wu Y, Rathore N, Tong RK, Peale F, Bagri A, Tessier-Lavigne M, Koch AW, Watts RJ. Neuropilin-1 binds to VEGF121 and regulates endothelial cell migration and sprouting. J Biol Chem. 2007;282:24049-56.
24. Liang WC, Dennis MS, Stawicki S, Chanthery Y, Pan Q, Chen Y, Eigenbrot C, Yin J, Koch AW, Wu X, Ferrara N, Bagri A, Tessier-Lavigne M, Watts RJ, Wu Y. Function blocking antibodies to neuropilin-1 generated from a designed human synthetic antibody phage library. J Mol Biol. 2007;366:815-29.
25. Pan Q, Chanthery Y, Liang WC, Stawicki S, Mak J, Rathore N, Tong RK, Kowalski J, Yee SF, Pacheco G, Ross S, Cheng Z, Le Couter J, Plowman G, Peale F, Koch AW, Wu Y, Bagri A, Tessier-Lavigne M, Watts RJ. Blocking neuropilin-1 function has an additive effect with anti-VEGF to inhibit tumor growth. Cancer Cell. 2007;11:53-67.
26. Xin Y, Xiang H, Dresser M, Brachmann RK, Bai S. Characterization of MNRP1685A (anti-NRP1) Clinical Pharmacokinetics in a first-in-human Phase I Study. AAPS National Biotechnology Conference (2010).
27. Gibiansky L, Gibiansky E, Kakkar T, Ma P. Approximations of the target-mediated drug disposition model and identifiability of model parameters. J Pharmacokinet Pharmacodyn. 2008;35:573-91.
28. Dedrick RL. Animal scale-up. J Pharmacokinet Biopharm. 1973;1:435-61.
29. Lu JF, Bruno R, Eppler S, Novotny W, Lum B, Gaudreault J. Clinical pharmacokinetics of bevacizumab in patients with solid tumors. Cancer Chemother Pharmacol. 2008;62:779-86.
30. Bruno R, Washington CB, Lu JF, Lieberman G, Banken L, Klein P. Population pharmacokinetics of trastuzumab in patients with HER2+ metastatic breast cancer. Cancer Chemother Pharmacol. 2005;56:361-9.
31. Ng CM, Lum BL, Gimenez V, Kelsey S, Allison D. Rationale for fixed dosing of pertuzumab in cancer patients based on population pharmacokinetic analysis. Pharm Res. 2006;23:1275-84.
32. Bumbaca D, Xiang H, Boswell CA, Port RE, Stainton SL, Mundo EE, Ulufatu S, Bagri A, Theil FP, Fielder PJ, Khawli LA, Shen BQ. Maximizing tumor exposure to anti-neuropilin-1 antibody requires saturation of non-tumor tissue antigenic sinks in mice. Br J Pharmacol. 2012;166:368-77.
33. Ma P, Yang BB, Wang YM, Peterson M, Narayanan A, Sutjandra L, Rodriguez R, Chow A. Population pharmacokinetic analysis of panitumumab in patients with advanced solid tumors. J Clin Pharmacol. 2009;49:1142-56.
34. Kloft C, Graefe EU, Tanswell P, Scott AM, Hofheinz R, Amelsberg A, Karlsson MO. Population pharmacokinetics of sibrotuzumab, a novel therapeutic monoclonal antibody, in cancer patients. Invest New Drugs. 2004;22:39-52.
35. Hansel DE, Wilentz RE, Yeo CJ, Schulick RD, Montgomery E, Maitra A. Expression of neuropilin-1 in high-grade dysplasia, invasive cancer, and metastases of the human gastrointestinal tract. Am J Surg Pathol. 2004;28:347-56.
36. Darbonne WC, Du X, Dhawan P, Hartley D, Tarrant J, Taylor H, Cain G, Shih LM, Brachmann RK, Phung Q, Weekes CD, LoRusso P, Patnaik A, Xiang H, Ramakrishnan V. Mechanism for platelet reduction in anti-neuropilin-1 (MNRP1685A)-treated phase I patients. J Clin Oncol. 2011, 29: Suppl; abstr e13598.