In vitro-in vivo correlations of pharmacokinetics, pharmacodynamics, and metabolism for antibody therapeutics

Proteins and Peptides: Pharmacokinetic, Pharmacodynamic, and Metabolic Outcomes

Volumn , Issue , 2009, Pages 15-52

  Boswell, C Andrew ^a   Deng, Rong ^a   Lin, Kedan ^a   Putnam, Wendy S ^a   Lei, Cherry ^a   Theil, Frank Peter ^a   Joshi, Amita ^a   Fielder, Paul J ^a   Khawli, Leslie A ^a  

^a GENENTECH INC   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

EID: 84964426438     PISSN: None     EISSN: None     Source Type: Book    
DOI: None     Document Type: Chapter

References (155)

1. Whitebread S, Hamon J, Bojanic D, et al. Keynote review: in vitro safety pharmacology profiling: an essential tool for successful drug development. Drug Discov Today 2005; 10(21):1421-1433.
2. Li AP. Screening for human ADME/Tox drug properties in drug discovery. Drug Discov Today 2001; 6(7):357-366.
3. Mager DE. Target-mediated drug disposition and dynamics. Biochem Pharmacol 2006; 72(1):1-10.
4. Theil FP, Guentert TW, Haddad S, et al. Utility of physiologically based pharmacokinetic models to drug development and rational drug discovery candidate selection. Toxicol Lett 2003; 138(1-2):29-49.
5. Lave T, Parrott N, Grimm HP, et al. Challenges and opportunities with modelling and simulation in drug discovery and drug development. Xenobiotica 2007; 37(10-11):1295-1310.
6. Day ED, Rigsbee LC, Rosenthal JT, et al. Adsorption properties in vitro and in vivo of antibodies raised against Rat brain blood vessels. J Immunol 1974; 112(2):607-616.
7. Mire-Sluis AR. Progress in the use of biological assays during the development of biotechnology products. Pharm Res 2001; 18(9):1239-1246.
8. Gunaratna C. Drug metabolism and pharmacokinetics in drug discovery: a primer for bioanalytical chemists, part I. Curr Separations 2000; 19(1):17-23.
9. Gunaratna C. Drug metabolism and pharmacokinetics in drug discovery: a primer for bioanalytical chemists, part II. Curr Separations 2001; 19(3):87-92.
10. Leveque D, Wisniewski S, Jehl F. Pharmacokinetics of therapeutic monoclonal antibodies used in oncology. Anticancer Res 2005; 25(3c):2327-2343.
11. Lobo ED, Hansen RJ, Balthasar JP. Antibody pharmacokinetics and pharmacodynamics. J Pharma Sci 2004; 93(11):2645-2668.
12. Boswell CA, Brechbiel MW. Development of radioimmunotherapeutic and diagnostic antibodies: an inside-out view. Nucl Med Biol 2007; 34(7):757-778.
13. Milenic DE, Brady ED, Brechbiel MW. Antibody-targeted radiation cancer therapy. Nat Rev Drug Discov 2004; 3(6):488-499.
14. Walsh G. Biopharmaceutical benchmarks 2006. Nat Biotechnol 2006; 24(7):769-776.
15. Epstein AL, Khawli LA. Tumor biology and monoclonal antibodies: overview of basic principles and clinical considerations. Antibody Immunoconj and Radiopharmacol 1991; 4:373-383.
16. Epstein AL, Khawli LA. Tumor necrosis therapy of cancer: new methods of antibody targeting. In: Henkin RE, Bova D, Dillehay GL, et al. eds. Nuclear Medicine: Principles & Practice. 2nd ed. Philadelpha: Mosby-Elsevier, 2006.
17. Roskos LK, Davis CG, Schwab GM. The clinical pharmacology of therapeutic monoclonal antibodies. Drug Dev Res 2004; 61(3):108-120.
18. Scallon BJ, Snyder LA, Anderson GM, et al. A review of antibody therapeutics and antibody-related technologies for oncology. J Immunother 2006; 29(4):351-364.
19. The PyMOL Molecular Graphics System. DeLano Scientific, 2002. Available at: http://www.pymol.org.
20. Ghetie V. The neonatal Fc receptor is a regulator of the homeostasis of IgG. Curr Trends Immunol 2006; 7:31-46.
21. Christiansen J, Rajasekaran AK. Biological impediments to monoclonal antibodybased cancer immunotherapy. Mol Cancer Ther 2004; 3(11):1493-1501.
22. Kohler G, Milstein C. Continuous cultures of fused cells secreting antibody of predefined specificity. Nature 1975; 256:495-497.
23. Khazaeli MB, Conry RM, LoBuglio AF. Human immune response to monoclonal antibodies. J Immunother Emphasis Tumor Immunol 1994; 15(1):42-52.
24. Oldham RK, Dillman RO. Monoclonal antibodies in cancer therapy: 25 years of progress. J Clin Oncol 2008; 26(11):1774-1777.
25. Kim SJ, Park Y, Hong HJ. Antibody engineering for the development of therapeutic antibodies. Mol Cells 2005; 20(1):17-29.
26. Holliger P, Hudson PJ. Engineered antibody fragments and the rise of single domains. Nat Biotechnol 2005; 23(9):1126-1136.
27. Holliger P, Prospero T, Winter G. “Diabodies”: small bivalent and bispecific antibody fragments. Proc Natl Acad Sci U S A 1993; 90(14):6444-6448.
28. Hudson PJ, Kortt AA. High avidity scFv multimers; diabodies and triabodies. J Immunol Methods 1999; 231(1-2):177-189.
29. Presta L. Antibody engineering for therapeutics. Curr Opin Struct Biol 2003; 13(4): 519-525.
30. Albrecht H, DeNardo SJ. Recombinant antibodies: from the laboratory to the clinic. Cancer Biother Radiopharm 2006; 21(4):285-304.
31. Wu AM, Senter PD. Arming antibodies: prospects and challenges for immunoconjugates. Nat Biotechnol 2005; 23(9):1137-1146.
32. Shen WC, Persiani S, Srivastava K. Chemical linkages in drug-antibody conjugation. BioPharm 1990; 3(1):16-22.
33. Vaidyanathan G, Zalutsky MR. Preparation of N-succinimidyl 3-[*I]iodobenzoate: an agent for the indirect radioiodination of proteins. Nat Protoc 2006; 1(2):707-713.
34. Larson SM. Radiolabeled monoclonal anti-tumor antibodies in diagnosis and therapy. J Nucl Med 1985; 26(5):538-545.
35. van Dongen GA, Visser GW, Lub-de Hooge MN, et al. Immuno-PET: a navigator in monoclonal antibody development and applications. Oncologist 2007; 12(12): 1379-1389.
36. Keller L, Boswell CA, Milenic DE, et al. Monoclonal antibody targeted radiation cancer therapy. In: Boehncke WH, Radeke HH, eds. Biologics in General Medicine. Berlin: Springer, 2007:50-58.
37. Beckman RA, Weiner LM, Davis HM. Antibody constructs in cancer therapy: protein engineering strategies to improve exposure in solid tumors. Cancer 2007; 109(2):170-179.
38. Joshi A, Bauer R, Kuebler P, et al. An overview of the pharmacokinetics and pharmacodynamics of efalizumab: a monoclonal antibody approved for use in psoriasis. J Clin Pharmacol 2006; 46(1):10-20.
39. Coffey GP, Stefanich E, Palmieri S, et al. In vitro internalization, intracellular transport, and clearance of an anti-CD11a antibody (Raptiva) by human T-cells. J Pharmacol Exp Ther 2004; 310(3):896-904.
40. Coffey GP, Fox JA, Pippig S, et al. Tissue distribution and receptor-mediated clearance of anti-CD11a antibody in mice. Drug Metab Dispos 2005; 33(5):623-629.
41. Sautes-Fridman C, Cassard L, Cohen-Solal J, et al. Fc gamma receptors: a magic link with the outside world. In: ASHI Quarterly: American Society for Histocompatibility and Immunogenetics, 2003:148-151.
42. Shields RL, Namenuk AK, Hong K, et al. High resolution mapping of the binding site on human IgG1 for Fc gamma RI, Fc gamma RII, Fc gamma RIII, and FcRn and design of IgG1 variants with improved binding to the Fc gamma R. J Biol Chem 2001; 276(9):6591-6604.
43. Gillies SD, Lan Y, Lo KM, et al. Improving the efficacy of antibody-interleukin 2 fusion proteins by reducing their interaction with Fc receptors. Cancer Res 1999; 59(9):2159-2166.
44. Hutchins JT, Kull FC Jr., Bynum J, et al. Improved biodistribution, tumor targeting, and reduced immunogenicity in mice with a gamma 4 variant of Campath-1H. Proc Natl Acad Sci U S A 1995; 92(26):11980-11984.
45. Sharma A, Davis CB, Tobia LA, et al. Comparative pharmacodynamics of keliximab and clenoliximab in transgenic mice bearing human CD4. J Pharmacol Exp Ther 2000; 293(1):33-41.
46. Kanda Y, Yamada T, Mori K, et al. Comparison of biological activity among nonfucosylated therapeutic IgG1 antibodies with three different N-linked Fc oligosaccharides: the high-mannose, hybrid, and complex types. Glycobiology 2007; 17(1):104-118.
47. Mannik M, Arend MP, Hall AP, et al. Studies on antigen-antibody complexes. I. Elimination of soluble complexes from rabbit circulation. J Exp Med 1971; 133(4): 713-739.
48. Ghetie V, Hubbard JG, Kim JK, et al. Abnormally short serum half-lives of IgG in beta 2-microglobulin-deficient mice. Eur J Immunol 1996; 26(3):690-696.
49. Junghans RP, Anderson CL. The protection receptor for IgG catabolism is the beta2-microglobulin-containing neonatal intestinal transport receptor. Proc Natl Acad Sci U S A 1996; 93(11):5512-5516.
50. Junghans RP. Finally! The Brambell receptor (FcRB). Mediator of transmission of immunity and protection from catabolism for IgG. Immunol Res 1997; 16(1):29-57.
51. Brambell F, Hemmings W, Morris I. A theoretical model of gamma-globulin catabloism. Nature 1964; 203:1352-1355.
52. Simister NE, Mostov KE. Cloning and expression of the neonatal rat intestinal Fc receptor, a major histocompatibility complex class I antigen homolog. Cold Spring Harb Symp Quant Biol 1989; 54(pt 1):571-580.
53. Simister NE, Mostov KE. An Fc receptor structurally related to MHC class I antigens. Nature 1989; 337(6203):184-187.
54. Roopenian DC, Christianson GJ, Sproule TJ, et al. The MHC class I-like IgG receptor controls perinatal IgG transport, IgG homeostasis, and fate of IgG-Fc-coupled drugs. J Immunol 2003; 170(7):3528-3533.
55. Medesan C, Matesoi D, Radu C, et al. Delineation of the amino acid residues involved in transcytosis and catabolism of mouse IgG1. J Immunol 1997; 158(5): 2211-2217.
56. Ober RJ, Radu CG, Ghetie V, et al. Differences in promiscuity for antibody-FcRn interactions across species: implications for therapeutic antibodies. Int Immunol 2001; 13(12):1551-1559.
57. Petkova SB, Akilesh S, Sproule TJ, et al. Enhanced half-life of genetically engineered human IgG1 antibodies in a humanized FcRn mouse model: potential application in humorally mediated autoimmune disease. Int Immunol 2006; 18(12):1759-1769.
58. Jaggi JS, Carrasquillo JA, Seshan SV, et al. Improved tumor imaging and therapy via i.v. IgG-mediated time-sequential modulation of neonatal Fc receptor. J Clin Invest 2007; 117(9):2422-2430.
59. Zhou J, Johnson JE, Ghetie V, et al. Generation of mutated variants of the human form of the MHC class I-related receptor, FcRn, with increased affinity for mouse immunoglobulin G. J Mol Biol 2003; 332(4):901-913.
60. Vaccaro C, Bawdon R, Wanjie S, et al. Divergent activities of an engineered antibody in murine and human systems have implications for therapeutic antibodies. Proc Natl Acad Sci U S A 2006; 103(49):18709-18714.
61. Hinton PR, Xiong JM, Johlfs MG, et al. An engineered human IgG1 antibody with longer serum half-life. J Immunol 2006; 176(1):346-356.
62. Datta-Mannan A, Witcher DR, Tang Y, et al. Monoclonal antibody clearance. Impact of modulating the interaction of IgG with the neonatal Fc receptor. J Biol Chem 2007; 282(3):1709-1717.
63. Datta-Mannan A, Witcher DR, Tang Y, et al. Humanized IgG1 variants with differential binding properties to the neonatal Fc receptor: relationship to pharmacokinetics in mice and primates. Drug Metab Dispos 2007; 35(1):86-94.
64. Yeung YA, Leabman MK, Marvin JS, et al. Engineering Human IgG1 Affinity to Human Neonatal Fc Receptor: Impact of Affinity Improvement on Pharmacokinetics in Primates. J Immunol 2009; 182:7663-7671.
65. Dall’Acqua WF, WoodsRM, Ward ES, et al. Increasing the affinity of a human IgG1 for the neonatal Fc receptor: biological consequences. J Immunol 2002; 169(9):5171-5180.
66. Dall’AcquaWF, Kiener PA, Wu H. Properties of human IgG1s engineered for enhanced binding to the neonatal Fc receptor (FcRn). J Biol Chem 2006; 281(33): 23514-23524.
67. Nicholson JP, Wolmarans MR, Park GR. The role of albumin in critical illness. Br J Anaesth 2000; 85(4):599-610.
68. Kratz F, Muller-Driver R, Hofmann I, et al. A novel macromolecular prodrug concept exploiting endogenous serum albumin as a drug carrier for cancer chemotherapy. J Med Chem 2000; 43(7):1253-1256.
69. Kurtzhals P, Havelund S, Jonassen I, et al. Albumin binding of insulins acylated with fatty acids: characterization of the ligand-protein interaction and correlation between binding affinity and timing of the insulin effect in vivo. Biochem J 1995; 312(pt 3):725-731.
70. Dennis MS, Jin H, Dugger D, et al. Imaging tumors with an albumin-binding Fab, a novel tumor-targeting agent. Cancer Res 2007; 67(1):254-261.
71. Dennis MS, Zhang M, Meng YG, et al. Albumin binding as a general strategy for improving the pharmacokinetics of proteins. J Biol Chem 2002, 277(38), 35035-35043.
72. Nguyen A, Reyes AE II, Zhang M, et al. The pharmacokinetics of an albuminbinding Fab (AB.Fab) can be modulated as a function of affinity for albumin. Protein Eng Des Sel 2006; 19(7):291-297.
73. Anderson CL, Chaudhury C, Kim J, et al. Perspective-FcRn transports albumin: relevance to immunology and medicine. Trends Immunol 2006; 27(7):343-348.
74. Khawli LA, Chen FM, Alauddin MM, et al. Radioiodinated monoclonal antibody conjugates: synthesis and comparative evaluation. Antibody Immunoconj Radiopharm 1991; 4:163-182.
75. Khawli LA, Glasky MS, Alauddin MM, et al. Improved tumor localization and radioimaging with chemically modified monoclonal antibodies. Cancer Biother Radiopharm 1996; 11(3):203-215.
76. Khawli LA, Mizokami MM, Sharifi J, et al. Pharmacokinetic characteristics and biodistribution of radioiodinated chimeric TNT-1, -2, and -3 monoclonal antibodies after chemical modification with biotin. Cancer Biother Radiopharm 2002; 17(4):359-370.
77. Chen S, Yu L, Jiang C, et al. Pivotal study of iodine-131-labeled chimeric tumor necrosis treatment radioimmunotherapy in patients with advanced lung cancer. J Clin Oncol 2005; 23(7):1538-1547.
78. Yu L, Ju DW, Chen W, et al. 131I-chTNT radioimmunotherapy of 43 patients with advanced lung cancer. Cancer Biother Radiopharm 2006; 21(1):5-14.
79. Silva Filho FC, Santos AB, de Carvalho TM, et al. Surface charge of resident, elicited, and activated mouse peritoneal macrophages. J Leukoc Biol 1987; 41(2):143-149.
80. Lee HJ, Pardridge WM. Monoclonal antibody radiopharmaceuticals: cationization, pegylation, radiometal chelation, pharmacokinetics, and tumor imaging. Bioconjug Chem 2003; 14(3):546-553.
81. Khawli LA, Biela B, Hu P, et al. Comparison of recombinant derivatives of chimeric TNT-3 antibody for the radioimaging of solid tumors. Hybrid Hybridomics 2003; 22(1):1-9.
82. Khawli LA, Biela BH, Hu P, et al. Stable, genetically engineered F(ab’)(2) fragments of chimeric TNT-3 expressed in mammalian cells. Hybrid Hybridomics 2002; 21(1): 11-18.
83. Moin K, McIntyre OJ, Matrisian LM, et al. Fluorescent imaging of tumors. In: Shields AF, Price P, eds. In Vivo Imaging of Cancer Therapy. Totowa, NJ: Humana Press, Inc., 2007:281-302.
84. Shockley TR, Lin K, Sung C, et al. A quantitative analysis of tumor specific monoclonal antibody uptake by human melanoma xenografts: effects of antibody immunological properties and tumor antigen expression levels. Cancer Res 1992; 52(2):357-366.
85. Jain RK. Determinants of tumor blood flow: a review. Cancer Res 1988; 48(10):2641-2658.
86. Sung C, Youle RJ, Dedrick RL. Pharmacokinetic analysis of immunotoxin uptake in solid tumors: role of plasma kinetics, capillary permeability, and binding. Cancer Res 1990; 50(22):7382-7392.
87. Blumenthal RD, Osorio L, Ochakovskaya R, et al. Regulation of tumour drug delivery by blood flow chronobiology. Eur J Cancer 2000; 36(14):1876-1884.
88. Lewis MR, Boswell CA, Laforest R, et al. Conjugation of monoclonal antibodies with TETA using activated esters: biological comparison of 64Cu-TETA-1A3 with 64Cu-BAT-2IT-1A3. Cancer Biother Radiopharm 2001; 16(6):483-494.
89. Rodwell JD, Alvarez VL, Lee C, et al. Site-specific covalent modification of monoclonal antibodies: in vitro and in vivo evaluations. Proc Natl Acad Sci U S A 1986; 83(8):2632-2636.
90. Burvenich I, Schoonooghe S, Cornelissen B, et al. In vitro and in vivo targeting properties of iodine-123-or iodine-131-labeled monoclonal antibody 14C5 in a nonsmall cell lung cancer and colon carcinoma model. Clin Cancer Res 2005; 11(20): 7288-7296.
91. Zuckier LS, Berkowitz EZ, Sattenberg RJ, et al. Influence of affinity and antigen density on antibody localization in a modifiable tumor targeting model. Cancer Res 2000; 60(24):7008-7013.
92. Sakahara H, Endo K, Koizumi M, et al. Relationship between in vitro binding activity and in vivo tumor accumulation of radiolabeled monoclonal antibodies. J Nucl Med 1988; 29(2):235-240.
93. Ng CM, Stefanich E, Anand BS, et al. Pharmacokinetics/pharmacodynamics of nondepleting anti-CD4 monoclonal antibody (TRX1) in healthy human volunteers. Pharm Res 2006; 23(1):95-103.
94. Worn A, Auf der Maur A, Escher D, et al. Correlation between in vitro stability and in vivo performance of anti-GCN4 intrabodies as cytoplasmic inhibitors. J Biol Chem 2000; 275(4):2795-2803.
95. Hochhaus G, Brookman L, Fox H, et al. Pharmacodynamics of omalizumab: implications for optimised dosing strategies and clinical efficacy in the treatment of allergic asthma. Curr Med Res Opin 2003; 19(6):491-498.
96. Liu J, Lester P, Builder S, et al. Characterization of complex formation by humanized anti-IgE monoclonal antibody and monoclonal human IgE. Biochemistry 1995; 34(33): 10474-10482.
97. Fox JA, Hotaling TE, Struble C, et al. Tissue distribution and complex formation with IgE of an anti-IgE antibody after intravenous administration in cynomolgus monkeys. J Pharmacol Exp Ther 1996; 279(2):1000-1008.
98. Schulman ES. Development of a monoclonal anti-immunoglobulin E antibody (omalizumab) for the treatment of allergic respiratory disorders. Am J Respir Crit Care Med 2001; 164(8 pt 2):S6-S11.
99. Putnam WS, Li J, Haggstrom J, et al. Use of quantitative pharmacology in the development of HAE1, a high-affinity anti-IgE monoclonal antibody. AAPS J 2008; 10(2):425-430.
100. Clarke J, Leach W, Pippig S, et al. Evaluation of a surrogate antibody for preclinical safety testing of an anti-CD11a monoclonal antibody. Regul Toxicol Pharmacol 2004; 40(3):219-226.
101. Smith MR. Rituximab (monoclonal anti-CD20 antibody): mechanisms of action and resistance. Oncogene 2003; 22(47):7359-7368.
102. Daniel D, Yang B, Lawrence DA, et al. Cooperation of the proapoptotic receptor agonist rhApo2L/TRAIL with the CD20 antibody rituximab against non-Hodgkin lymphoma xenografts. Blood 2007; 110(12):4037-4046.
103. Zhang N, Khawli LA, Hu P, et al. Generation of rituximab polymer may cause hyper-cross-linking-induced apoptosis in non-Hodgkin’s lymphomas. Clin Cancer Res 2005; 11(16):5971-5980.
104. Byrd JC, Kitada S, Flinn IW, et al. The mechanism of tumor cell clearance by rituximab in vivo in patients with B-cell chronic lymphocytic leukemia: evidence of caspase activation and apoptosis induction. Blood 2002; 99(3):1038-1043.
105. Borchmann P, Treml JF, Hansen H, et al. The human anti-CD30 antibody 5F11 shows in vitro and in vivo activity against malignant lymphoma. Blood 2003; 102(10):3737-3742.
106. Kelley SK, Gelzleichter T, Xie D, et al. Preclinical pharmacokinetics, pharmacodynamics, and activity of a humanized anti-CD40 antibody (SGN-40) in rodents and non-human primates. Br J Pharmacol 2006; 148(8):1116-1123.
107. Baselga J, Perez EA, Pienkowski T, et al. Adjuvant trastuzumab: a milestone in the treatment of HER-2-positive early breast cancer. Oncologist 2006; 11(suppl 1):4-12.
108. Mann M, Sheng H, Shao J, et al. Targeting cyclooxygenase 2 and HER-2/neu pathways inhibits colorectal carcinoma growth. Gastroenterology 2001; 120(7):1713-1719.
109. Agus DB, Akita RW, Fox WD, et al. Targeting ligand-activated ErbB2 signaling inhibits breast and prostate tumor growth. Cancer Cell 2002; 2(2):127-137.
110. Lin BC, Wang M, Blackmore C, et al. Liver-specific activities of FGF19 require Klotho beta. J Biol Chem 2007; 282(37):27277-27284.
111. Desnoyers LR, Pai R, Ferrando RE, et al. Targeting FGF19 inhibits tumor growth in colon cancer xenograft and FGF19 transgenic hepatocellular carcinoma models. Oncogene 2008; 27(1):85-97.
112. Bell SJ, Kamm MA. Review article: the clinical role of anti-TNFalpha antibody treatment in Crohn’s disease. Aliment Pharmacol Ther 2000; 14(5):501-514.
113. Balkwill F. Tumor necrosis factor or tumor promoting factor? Cytokine Growth Factor Rev 2002; 13(2):135-141.
114. Mpofu S, Fatima F, Moots RJ. Anti-TNF-alpha therapies: they are all the same (aren’t they?). Rheumatology (Oxford) 2005; 44(3):271-273.
115. Egberts JH, Cloosters V, Noack A, et al. Anti-tumor necrosis factor therapy inhibits pancreatic tumor growth and metastasis. Cancer Res 2008; 68(5):1443-1450.
116. Teng MN, Park BH, Koeppen HK, et al. Long-term inhibition of tumor growth by tumor necrosis factor in the absence of cachexia or T-cell immunity. Proc Natl Acad Sci U S A 1991; 88(9):3535-3539.
117. Bromberg JS, Chavin KD, Kunkel SL. Anti-tumor necrosis factor antibodies suppress cell-mediated immunity in vivo. J Immunol 1992; 148(11):3412-3417.
118. Waterston AM, Salway F, Andreakos E, et al. TNF autovaccination induces self anti-TNF antibodies and inhibits metastasis in a murine melanoma model. Br J Cancer 2004; 90(6):1279-1284.
119. Ferrara N, Hillan KJ, Gerber HP, et al. Discovery and development of bevacizumab, an anti-VEGF antibody for treating cancer. Nat Rev Drug Discov 2004; 3(5): 391-400.
120. Bhaskara A, Eng C. Bevacizumab in the treatment of a patient with metastatic colorectal carcinoma with brain metastases. Clin Colorectal Cancer 2008; 7(1):65-68.
121. Scott LJ. Bevacizumab: in first-line treatment of metastatic breast cancer. Drugs 2007; 67(12):1793-1799.
122. Manegold C. Bevacizumab for the treatment of advanced non-small-cell lung cancer. Expert Rev Anticancer Ther 2008; 8(5):689-699.
123. Gerber HP, Wu X, Yu L, et al. Mice expressing a humanized form of VEGF-A may provide insights into the safety and efficacy of anti-VEGF antibodies. Proc Natl Acad Sci U S A 2007; 104(9):3478-3483.
124. Gaudreault J, Fei D, Rusit J, et al. Preclinical pharmacokinetics of Ranibizumab (rhuFabV2) after a single intravitreal administration. Invest Ophthalmol Vis Sci 2005; 46(2):726-733.
125. Lowe J, Araujo J, Yang J, et al. Ranibizumab inhibits multiple forms of biologically active vascular endothelial growth factor in vitro and in vivo. Exp Eye Res 2007; 85(4):425-430.
126. Sands H, Jones PL. Methods for the study of the metabolism of radiolabeled monoclonal antibodies by liver and tumor. J Nucl Med 1987; 28(3):390-398.
127. Rogers BE, Franano FN, Duncan JR, et al. Identification of metabolites of 111Indiethylenetriaminepentaacetic acid-monoclonal antibodies and antibody fragments in vivo. Cancer Res 1995; 55(23 suppl):5714s-5720s.
128. Tsai SW, Li L, Williams LE, et al. Metabolism and renal clearance of 111In-labeled DOTA-conjugated antibody fragments. Bioconjug Chem 2001; 12(2):264-270.
129. Schwartz RS. Paul Ehrlich’s magic bullets. N Engl J Med 2004; 350(11):1079-1080.
130. Schrama D, Reisfeld RA, Becker JC. Antibody targeted drugs as cancer therapeutics. Nat Rev Drug Discov 2006; 5(2):147-159.
131. McCarron PA, Olwill SA, Marouf WM, et al. Antibody conjugates and therapeutic strategies. Mol Interv 2005; 5(6):368-380.
132. Garnett MC. Targeted drug conjugates: principles and progress. Adv Drug Deliv Rev 2001; 53(2):171-216.
133. Maxfield FR, McGraw TE. Endocytic recycling. Nat Rev Mol Cell Biol 2004; 5(2): 121-132.
134. Yelton DE, Scharff MD. Monoclonal antibodies: a powerful new tool in biology and medicine. Annu Rev Biochem 1981; 50:657-680.
135. Beeram M. A phase i study of trastuzumab-DM1, a first-in-class HER2 antibodydrug conjugate (ADC), in patients with advanced HER2-positive breast cancer (abstract 1028). 44th Annual Meeting of the American Society of Clinical Oncology (ASCO), 2008, Chicago, IL.
136. Doronina SO, Mendelsohn BA, Bovee TD, et al. Enhanced activity of monomethylauristatin F through monoclonal antibody delivery: effects of linker technology on efficacy and toxicity. Bioconjug Chem 2006; 17(1):114-124.
137. Guillemard V, Saragovi HU. Novel approaches for targeted cancer therapy. Curr Cancer Drug Targets 2004; 4(4):313-326.
138. Reff M, Braslawsky G, Hanna N. Future approaches for treating hematologic disease. Curr Pharm Biotechnol 2001; 2(4):369-382.
139. Berek JS, Thomas GM, Ozols RF. Ovarian cancer. In: Holland JF, Frei E, Bast RC, eds. Oncology: Principles and Practice. 2nd ed. Philadelphia: Lippincott, 1996.
140. Chen Y, Clark S, Wong T, et al. Armed antibodies targeting the mucin repeats of the ovarian cancer antigen, MUC16, are highly efficacious in animal tumor models. Cancer Res 2007; 67(10):4924-4932.
141. Ross S, Spencer SD, Holcomb I, et al. Prostate stem cell antigen as therapy target: tissue expression and in vivo efficacy of an immunoconjugate. Cancer Res 2002; 62(9):2546-2553.
142. Mao W, Luis E, Ross S, et al. EphB2 as a therapeutic antibody drug target for the treatment of colorectal cancer. Cancer Res 2004; 64(3):781-788.
143. Polson AG, Yu SF, Elkins K, et al. Antibody-drug conjugates targeted to CD79 for the treatment of non-Hodgkin lymphoma. Blood 2007; 110(2):616-623.
144. Hamblett KJ, Senter PD, Chace DF, et al. Effects of drug loading on the antitumor activity of a monoclonal antibody drug conjugate. Clin Cancer Res 2004; 10(20): 7063-7070.
145. Erickson HK, Park PU, Widdison WC, et al. Antibody-maytansinoid conjugates are activated in targeted cancer cells by lysosomal degradation and linker-dependent intracellular processing. Cancer Res 2006; 66(8):4426-4433.
146. Sutherland MS, Sanderson RJ, Gordon KA, et al. Lysosomal trafficking and cysteine protease metabolism confer target-specific cytotoxicity by peptide-linked anti-CD30-auristatin conjugates. J Biol Chem 2006; 281(15):10540-10547.
147. Alley SC, Benjamin DR, Jeffrey SC, et al. Contribution of linker stability to the activities of anticancer immunoconjugates. Bioconjug Chem 2008; 19(3):759-765.
148. Doronina SO, Toki BE, Torgov MY, et al. Development of potent monoclonal antibody auristatin conjugates for cancer therapy. Nat Biotechnol 2003; 21(7):778-784.
149. Kovtun YV, Audette CA, Ye Y, et al. Antibody-drug conjugates designed to eradicate tumors with homogeneous and heterogeneous expression of the target antigen. Cancer Res 2006; 66(6):3214-3221.
150. Kovtun YV, Goldmacher VS. Cell killing by antibody-drug conjugates. Cancer Lett 2007; 255(2):232-240.
151. Ng CM, Joshi A, Dedrick RL, et al. Pharmacokinetic-pharmacodynamic-efficacy analysis of efalizumab in patients with moderate to severe psoriasis. Pharm Res 2005; 22(7):1088-1100.
152. Meijer RT, Koopmans RP, ten Berge IJ, et al. Pharmacokinetics of murine antihuman CD3 antibodies in man are determined by the disappearance of target antigen. J Pharmacol Exp Ther 2002; 300(1):346-353.
153. Bauer RJ, Dedrick RL, White ML, et al. Population pharmacokinetics and pharmacodynamics of the anti-CD11a antibody hu1124 in human subjects with psoriasis. J Pharmacokinet Biopharm 1999; 27(4):397-420.
154. Ricart AD, Tolcher AW. Technology insight: cytotoxic drug immunoconjugates for cancer therapy. Nat Clin Pract Oncol 2007; 4(4):245-255.
155. Wong DF. Imaging in drug discovery, preclinical, and early clinical development. J Nucl Med 2008; 49(6):26N-28N.