Conjugation of 10 kDa Linear PEG onto Trastuzumab Fab′ Is Sufficient to Significantly Enhance Lymphatic Exposure while Preserving in Vitro Biological Activity

Molecular Pharmaceutics

Volumn 13, Issue 4, 2016, Pages 1229-1241

  Chan, Linda J ^a   Ascher, David B ^b   Yadav, Rajbharan ^a   Bulitta, Jürgen B ^a,c   Williams, Charlotte C ^d   Porter, Christopher J H ^a   Landersdorfer, Cornelia B ^a   Kaminskas, Lisa M ^a  

^a MONASH UNIVERSITY   (Australia)

^b UNIVERSITY OF CAMBRIDGE   (United Kingdom)

^c UNIVERSITY OF FLORIDA   (United States)

^d CSIRO   (Australia)

Author keywords

Fab; lymphatic; monoclonal antibody; PEGylation; pharmacokinetics; population modeling; S ADAPT; trastuzumab

Indexed keywords

EPIDERMAL GROWTH FACTOR RECEPTOR 2; IMMUNOGLOBULIN F(AB) FRAGMENT; MACROGOL; MONOCLONAL ANTIBODY; TRASTUZUMAB; MACROGOL DERIVATIVE;

ANIMAL EXPERIMENT; ANTIPROLIFERATIVE ACTIVITY; ARTICLE; CONTROLLED STUDY; DRUG ABSORPTION; DRUG CLEARANCE; DRUG CONJUGATION; DRUG ELIMINATION; DRUG HALF LIFE; DRUG RECEPTOR BINDING; HUMAN; HUMAN CELL; IN VITRO STUDY; LYMPHATIC SYSTEM; MALE; MEAN TRANSIT TIME; MOLECULAR WEIGHT; NONHUMAN; PHARMACOKINETIC PARAMETERS; PRIORITY JOURNAL; PROTEIN EXPRESSION; RAT; RECEPTOR AFFINITY; THORACIC DUCT; VOLUME OF DISTRIBUTION; ANIMAL; CHEMISTRY; IMMUNOLOGY; SIZE EXCLUSION CHROMATOGRAPHY; SPRAGUE DAWLEY RAT; TUMOR CELL LINE;

ANIMALS; ANTIBODIES, MONOCLONAL; CELL LINE, TUMOR; CHROMATOGRAPHY, GEL; HUMANS; IMMUNOGLOBULIN FAB FRAGMENTS; MALE; POLYETHYLENE GLYCOLS; RATS; RATS, SPRAGUE-DAWLEY; TRASTUZUMAB;

EID: 84963828918     PISSN: 15438384     EISSN: 15438392     Source Type: Journal    
DOI: 10.1021/acs.molpharmaceut.5b00749     Document Type: Article

References (37)

1. Nelson, A. L.; Dhimolea, E.; Reichert, J. M. Development trends for human monoclonal antibody therapeutics Nat. Rev. Drug Discovery 2010, 9 (10) 767-74 10.1038/nrd3229
2. Chames, P.; Van Regenmortel, M.; Weiss, E.; Baty, D. Therapeutic antibodies: successes, limitations and hopes for the future Br. J. Pharmacol. 2009, 157 (2) 220-33 10.1111/j.1476-5381.2009.00190.x
3. Chapman, A. P. PEGylated antibodies and antibody fragments for improved therapy: a review Adv. Drug Delivery Rev. 2002, 54 (4) 531-45 10.1016/S0169-409X(02)00026-1
4. Wang, W.; Wang, E. Q.; Balthasar, J. P. Monoclonal antibody pharmacokinetics and pharmacodynamics Clin. Pharmacol. Ther. 2008, 84 (5) 548-58 10.1038/clpt.2008.170
5. Dahlberg, A. M.; Kaminskas, L. M.; Smith, A.; Nicolazzo, J. A.; Porter, C. J. H.; Bulitta, J. B.; McIntosh, M. P. The lymphatic system plays a major role in the intravenous and subcutaneous pharmacokinetics of trastuzumab in rats Mol. Pharmaceutics 2014, 11 (2) 496-504 10.1021/mp400464s
6. Chan, L. J.; Bulitta, J. B.; Ascher, D. B.; Haynes, J. M.; McLeod, V. M.; Porter, C. J.H.; Williams, C. C.; Kaminskas, L. M. PEGylation does not significantly change the initial intravenous or subcutaneous pharmacokinetics or lymphatic exposure of trastuzumab in rats but increases plasma clearance after subcutaneous administration Mol. Pharmaceutics 2015, 12 (3) 794-809 10.1021/mp5006189
7. Weiner, L. M.; Surana, R.; Wang, S. Monoclonal antibodies: versatile platforms for cancer immunotherapy Nat. Rev. Immunol. 2010, 10 (5) 317-27 10.1038/nri2744
8. Faulds, D.; Sorkin, E. M. Abciximab (c7E3 Fab). A review of its pharmacology and therapeutic potential in ischaemic heart disease Drugs 1994, 48 (4) 583-98 10.2165/00003495-199448040-00007
9. Rosenfeld, P. J.; Brown, D. M.; Heier, J. S.; Boyer, D. S.; Kaiser, P. K.; Chung, C. Y.; Kim, R. Y.; Group, M. S. Ranibizumab for neovascular age-related macular degeneration N. Engl. J. Med. 2006, 355 (14) 1419-31 10.1056/NEJMoa054481
10. Melmed, G. Y.; Targan, S. R.; Yasothan, U.; Hanicq, D.; Kirkpatrick, P. Certolizumab pegol Nat. Rev. Drug Discovery 2008, 7 (8) 641-2 10.1038/nrd2654
11. Chapman, A. P.; Antoniw, P.; Spitali, M.; West, S.; Stephens, S.; King, D. J. Therapeutic antibody fragments with prolonged in vivo half-lives Nat. Biotechnol. 1999, 17 (8) 780-3 10.1038/11717
12. Nelson, A. L. Antibody fragments: hope and hype MAbs 2010, 2 (1) 77-83 10.4161/mabs.2.1.10786
13. Humphreys, D. P.; Heywood, S. P.; Henry, A.; Ait-Lhadj, L.; Antoniw, P.; Palframan, R.; Greenslade, K. J.; Carrington, B.; Reeks, D. G.; Bowering, L. C.; West, S.; Brand, H. A. Alternative antibody Fab′ fragment PEGylation strategies: combination of strong reducing agents, disruption of the interchain disulphide bond and disulphide engineering Protein Eng., Des. Sel. 2007, 20 (5) 227-34 10.1093/protein/gzm015
14. Neuber, T.; Frese, K.; Jaehrling, J.; Jager, S.; Daubert, D.; Felderer, K.; Linnemann, M.; Hohne, A.; Kaden, S.; Kolln, J.; Tiller, T.; Brocks, B.; Ostendorp, R.; Pabst, S. Characterization and screening of IgG binding to the neonatal Fc receptor MAbs 2014, 6 (4) 928-42 10.4161/mabs.28744
15. Trevaskis, N. L.; Kaminskas, L. M.; Porter, C. J. H. From sewer to saviour-targeting the lymphatic system to promote drug exposure and activity Nat. Rev. Drug Discovery 2015, 14 (11) 781-803 10.1038/nrd4608
16. Schlapschy, M.; Binder, U.; Borger, C.; Theobald, I.; Wachinger, K.; Kisling, S.; Haller, D.; Skerra, A. PASylation: a biological alternative to PEGylation for extending the plasma half-life of pharmaceutically active proteins Protein Eng., Des. Sel. 2013, 26 (8) 489-501 10.1093/protein/gzt023
17. Monfardini, C.; Veronese, F. M. Stabilization of substances in circulation Bioconjugate Chem. 1998, 9 (4) 418-50 10.1021/bc970184f
18. Kaminskas, L. M.; Ascher, D. B.; McLeod, V. M.; Herold, M. J.; Le, C. P.; Sloan, E. K.; Porter, C. J. H. PEGylation of interferon alpha2 improves lymphatic exposure after subcutaneous and intravenous administration and improves antitumour efficacy against lymphatic breast cancer metastases J. Controlled Release 2013, 168 (2) 200-8 10.1016/j.jconrel.2013.03.006
19. Jain, R. K. Physiological barriers to delivery of monoclonal antibodies and other macromolecules in tumors Cancer Res. 1990, 50 (3) 814s-819s
20. Yokota, T.; Milenic, D. E.; Whitlow, M.; Schlom, J. Rapid tumor penetration of a single-chain Fv and comparison with other immunoglobulin forms Cancer Res. 1992, 52 (12) 3402-8
21. Koussoroplis, S. J.; Paulissen, G.; Tyteca, D.; Goldansaz, H.; Todoroff, J.; Barilly, C.; Uyttenhove, C.; Van Snick, J.; Cataldo, D.; Vanbever, R. PEGylation of antibody fragments greatly increases their local residence time following delivery to the respiratory tract J. Controlled Release 2014, 187, 91-100 10.1016/j.jconrel.2014.05.021
22. McLennan, D. N.; Porter, C. J. H.; Edwards, G. A.; Martin, S. W.; Charman, S. A. Molecular weight is a primary determinant for lymphatic absorption of proteins following subcutaneous administration to sheep AAPS PharmSci. 2002, 4, W4041
23. Kaminskas, L. M.; Kota, J.; McLeod, V. M.; Kelly, B. D.; Karellas, P.; Porter, C. J. H. PEGylation of polylysine dendrimers improves absorption and lymphatic targeting following SC administration in rats J. Controlled Release 2009, 140 (2) 108-16 10.1016/j.jconrel.2009.08.005
24. Ascher, D. B.; Wielens, J.; Nero, T. L.; Doughty, L.; Morton, C. J.; Parker, M. W. Potent hepatitis C inhibitors bind directly to NS5A and reduce its affinity for RNA Sci. Rep. 2014, 4, 4765 10.1038/srep04765
25. Kaminskas, L. M.; Kelly, B. D.; McLeod, V. M.; Sberna, G.; Boyd, B. J.; Owen, D. J.; Porter, C. J. H. Capping methotrexate alpha-carboxyl groups enhances systemic exposure and retains the cytotoxicity of drug conjugated PEGylated polylysine dendrimers Mol. Pharmaceutics 2011, 8 (2) 338-49 10.1021/mp1001872
26. Khalili, H.; Godwin, A.; Choi, J. W.; Lever, R.; Brocchini, S. Comparative binding of disulfide-bridged PEG-Fabs Bioconjugate Chem. 2012, 23 (11) 2262-77 10.1021/bc300372r
27. Ryan, G. M.; Kaminskas, L. M.; Bulitta, J. B.; McIntosh, M. P.; Owen, D. J.; Porter, C. J.H. PEGylated polylysine dendrimers increase lymphatic exposure to doxorubicin when compared to PEGylated liposomal and solution formulations of doxorubicin J. Controlled Release 2013, 172 (1) 128-36 10.1016/j.jconrel.2013.08.004
28. Levy, G. Pharmacologic target-mediated drug disposition Clin. Pharmacol. Ther. 1994, 56 (3) 248-52 10.1038/clpt.1994.134
29. Mager, D. E.; Jusko, W. J. General pharmacokinetic model for drugs exhibiting target-mediated drug disposition J. Pharmacokinet. Pharmacodyn. 2001, 28 (6) 507-32 10.1023/A:1014414520282
30. Bulitta, J. B.; Bingolbali, A.; Shin, B. S.; Landersdorfer, C. B. Development of a new pre- and post-processing tool (SADAPT-TRAN) for nonlinear mixed-effects modeling in S-ADAPT AAPS J. 2011, 13 (2) 201-11 10.1208/s12248-011-9257-x
31. Bulitta, J. B.; Landersdorfer, C. B. Performance and robustness of the Monte Carlo importance sampling algorithm using parallelized S-ADAPT for basic and complex mechanistic models AAPS J. 2011, 13 (2) 212-26 10.1208/s12248-011-9258-9
32. Bauer, R. J.; Guzy, S.; Ng, C. A survey of population analysis methods and software for complex pharmacokinetic and pharmacodynamic models with examples AAPS J. 2007, 9 (1) E60-83 10.1208/aapsj0901007
33. Kawada, K.; Taketo, M. M. Significance and mechanism of lymph node metastasis in cancer progression Cancer Res. 2011, 71 (4) 1214-8 10.1158/0008-5472.CAN-10-3277
34. Ho, R. J.; Yu, J.; Li, B.; Kraft, J. C.; Freeling, J. P.; Koehn, J.; Shao, J. Systems Approach to targeted and long-acting HIV/AIDS therapy Drug Delivery Transl. Res. 2015, 5, 531 10.1007/s13346-015-0254-y
35. Sievers, S. A.; Scharf, L.; West, A. P., Jr.; Bjorkman, P. J. Antibody engineering for increased potency, breadth and half-life Curr. Opin. HIV AIDS 2015, 10 (3) 151-9 10.1097/COH.0000000000000148
36. Jackisch, C.; Muller, V.; Maintz, C.; Hell, S.; Ataseven, B. Subcutaneous Administration of Monoclonal Antibodies in Oncology Geburtshilfe Frauenheilkd. 2014, 74 (4) 343-349 10.1055/s-0034-1368173
37. Mezyk-Kopec, R.; Wyroba, B.; Stalinska, K.; Prochnicki, T.; Wiatrowska, K.; Kilarski, W. W.; Swartz, M. A.; Bereta, J. ADAM17 Promotes Motility, Invasion, and Sprouting of Lymphatic Endothelial Cells PLoS One 2015, 10 (7) e0132661 10.1371/journal.pone.0132661