Antibody-drug conjugates: Using monoclonal antibodies for delivery of cytotoxic payloads to cancer cells

Therapeutic Delivery

Volumn 2, Issue 3, 2011, Pages 397-416

  Goldmacher, Victor S ^a   Kovtun, Yelena V ^a  

^a IMMUNOGEN INC   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ANTIBODY CONJUGATE; BT 062; CALICHEAMICIN; CAMPTOTHECIN; CAMPTOTHECIN DERIVATIVE; CANTUZUMAB MERTANSINE; CETUXIMAB; CYTOTOXIC AGENT; DOLASTATIN; EPIDERMAL GROWTH FACTOR RECEPTOR 2; GEMTUZUMAB OZOGAMICIN; IMGN 388; IMMUNOGLOBULIN G1; IMMUNOGLOBULIN G3; IMMUNOGLOBULIN G4; INOTUZUMAB OZOGAMICIN; MAYTANSINE; MDX 1203; MEMBRANE ANTIGEN; MONOCLONAL ANTIBODY; PANITUMUMAB; RITUXIMAB; SAR 3419; SGN 30; SGN 75; SR 3419; TAXANE DERIVATIVE; TRASTUZUMAB; TUMOR ANTIGEN; UNCLASSIFIED DRUG; UNINDEXED DRUG;

ACUTE GRANULOCYTIC LEUKEMIA; ADVANCED CANCER; ANTIGEN ANTIBODY REACTION; ANTIGEN EXPRESSION; B CELL LYMPHOMA; BREAST CANCER; CANCER CELL; CANCER RESISTANCE; CANCER STEM CELL; CARCINOMA; DRUG CLEARANCE; DRUG CYTOTOXICITY; DRUG DELIVERY SYSTEM; DRUG HALF LIFE; DRUG MECHANISM; DRUG MEGADOSE; DRUG STABILITY; DRUG TARGETING; HUMAN; KIDNEY CARCINOMA; LIVER VENOOCCLUSIVE DISEASE; MALIGNANT NEOPLASTIC DISEASE; MAXIMUM TOLERATED DOSE; MELANOMA; MULTIDRUG RESISTANCE; MULTIPLE MYELOMA; NONHODGKIN LYMPHOMA; NONHUMAN; PRIORITY JOURNAL; RECURRENT CANCER; REVIEW; SARCOMA; SOLID TUMOR; TARGET CELL; TREATMENT RESPONSE;

EID: 79952660539     PISSN: 20415990     EISSN: 20416008     Source Type: Journal    
DOI: 10.4155/tde.10.98     Document Type: Review

References (214)

1. Pratt WB, Ruddon RW, Ensminger WD, et al. Part 2. The Anticancer Drugs. Oxford University Press, UK 69-198 (1994).
2. Scheinberg DA, Rosenblat TL, Jurcic JG et al. Antibodies. In: Chemotherapy and Biotherapy: Principles and Practice (Fifth Edition). Chabner BA, Longo DL (Eds). Wolters Kluwer/Lippincott Williams & Wilkins, Health, PA, USA 465-494 (2011).
3. Boyiadzis M, Foon KA. Approved monoclonal antibodies for cancer therapy. Expert Opin. Biol. Ther. 8(8), 1151-1158 (2008).
4. Reichert JM. Monoclonal antibodies in the clinic. Nat. Biotechnol. 19(9), 819-822 (2001). (Pubitemid 32816751)
5. Lambert JM. Antibody-maytansinoid conjugates: a new strategy for the treatment of cancer. Drugs Future 35(6), 471-480 (2010).
6. Senter PD. Potent antibody-drug conjugates for cancer therapy. Curr. Opin. Chem. Biol. 13 (3), 235-244 (2009).
7. Goldmacher VS, Blattler WA, Lambert JM, Chari RVJ. Immunotoxins and antibody-drug conjugates for cancer treatment. In: Biomedical Aspects of Drug Targeting Torchilin V, Muzykantov V (Eds). 291-309, Kluwer Academic Publishers, MA, USA (2002).
8. Chari RV. Targeted cancer therapy: conferring specifcity to cytotoxic drugs. Acc. Chem. Res. 41(1), 98-107 (2008).
9. Ducry L, Stump B. Antibody-drug conjugates: linking cytotoxic payloads to monoclonal antibodies. Bioconjug. Chem. 21(1), 5-13 (2010).
10. Kovtun YV, Goldmacher VS. Cell killing by antibody-drug conjugates. Cancer Lett. 255(2), 232-240 (2007). (Pubitemid 47268641)
11. Carter PJ, Senter PD. Antibody-drug conjugates for cancer therapy. Cancer J. 14(3), 154-169 (2008).
12. Vater AV, Goldmacher VS. Antibody-cytotoxic compound conjugates for oncology. In: Macromolecular Anticancer Therapeutics. Reddy LH, Couvreur P (Eds). Springer, NY, USA 331-369 (2009).
13. Henry MD, Wen S, Silva MD et al. A prostate-specifc membrane antigen-targeted monoclonal antibody-chemotherapeutic conjugate designed for the treatment of prostate cancer. Cancer Res. 64(21), 7995-8001 (2004). (Pubitemid 39446934)
14. Ma D, Hopf CE, Malewicz AD et al. Potent antitumor activity of an auristatin-conjugated, fully human monoclonal antibody to prostate-specifc membrane antigen. Clin. Cancer Res. 12(8), 2591-2596 (2006).
15. Galsky MD, Eisenberger M, Moore-Cooper S et al. Phase I trial of the prostate-specifc membrane antigen-directed immunoconjugate MLN2704 in patients with progressive metastatic castration-resistant prostate cancer. J. Clin. Oncol. 26(13), 2147-2154 (2008).
16. Pan C, Terrett J, Rao C et al. Human antibody conjugates of potential utility for prostate cancer therapy: a comparison of MGBA conjugates with antibodies targeting a cell surface target (prostate-specifc membrane antigen) and an extracellular matrix target (Mindin/RG-1). AACR Annual Meeting Abstracts 4062 (2008).
17. + metastatic breast cancer. Am. Soc. Clin. Onc. Annu. Meet. Proc. (2008) (Abstract #1028).
18. Burris HA, Vukelja S, Rugo HS et al. A Phase II study of trastuzumab-DM1 (T-DM1), a HER2 antibody-drug conjugate, in patients with HER2-positive metastatic breast cancer. ASCO Breast Cancer Symposium Proceedings (2008) (Abstract 155).
19. + breast cancer. Am. Soc. Clin. Onc. Annu. Meet. Proc. (2008) (Abstract 1029).
20. Press MF, Cordon-Cardo C, Slamon DJ. Expression of the HER2/neu proto-oncogene in normal human adult and fetal tissues. Oncogene 5(7), 953-962 (1990).
21. Carter P, Smith L, Ryan M. Identifcation and validation of cell surface antigens for antibody targeting in oncology. Endocr. Relat. Cancer 11(4), 659-687 (2004). (Pubitemid 40065544)
22. Xie H, Blattler WA. In vivo behavior of Antibody-drug conjugates for the targeted treatment of cancer. Expert Opin. Biol. Ther. 6(3), 281-291 (2006). (Pubitemid 43344746)
23. Kononen J, Bubendorf L, Kallioniemi A et al. Tissue microarrays for high-throughput molecular profling of tumor specimens. Nat. Med. 4(7), 844-847 (1998). (Pubitemid 28331029)
24. 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. 66(6), 3214-3221 (2006).
25. Liu C, Tadayoni BM, Bourret LA et al. Eradication of large colon tumor xenografts by targeted delivery of maytansinoids. Proc. Natl Acad. Sci. USA 93 (16), 8618-8623 (1996). (Pubitemid 26269609)
26. Bhaskar V, Law DA, Ibsen E et al. E-selectin up-regulation allows for targeted drug delivery in prostate cancer. Cancer Res. 63 (19), 6387-6394 (2003). (Pubitemid 37255188)
27. Walter RB, Raden BW, Kamikura DM et al. Infuence of CD33 expression levels and ITIM-dependent internalization on gemtuzumab ozogamicin-induced cytotoxicity. Blood 105 (3), 1295-1302 (2005). (Pubitemid 40170906)
28. Smith LM, Nesterova A, Alley SC et al. Potent cytotoxicity of an auristatin-containing antibody-drug conjugate targeting melanoma cells expressing melanotransferrin/p97 Mol. Cancer Ther. 5(6), 1474-1482 (2006). (Pubitemid 44070484)
29. Smith LM, Nesterova A, Ryan MC et al. CD133/prominin-1 is a potential therapeutic target for antibody-drug conjugates in hepatocellular and gastric cancers. Br. J. Cancer 99 (1), 100-109 (2008). (Pubitemid 351920235)
30. Ofazoglu E, Stone IJ, Gordon K et al. Potent anticarcinoma activity of the humanized anti-CD70 antibody h1F6 conjugated to the tubulin inhibitor auristatin via an uncleavable linker. Clin. Cancer Res. 14(19), 6171-6180 (2008).
31. Ingle GS, Chan P, Elliott JM et al. High CD21 expression inhibits internalization of anti-CD19 antibodies and cytotoxicity of an anti-CD19-drug conjugate. Br. J. Haematol. 140 (1), 46-58 (2008). (Pubitemid 350233252)
32. Polson AG, Williams M, Gray AM et al. Anti-CD22-MCC-DM1: an antibody-drug conjugate with a stable linker for the treatment of non-Hodgkin's lymphoma. Leukemia 24(9), 1566-1573 (2010).
33. Polson A. Antibody-drug conjugates for the treatment of non-Hodgkin's lymphoma. Presented at: The Drug Discovery and Development of Innovative Therapeutics Conference. Boston, MA, USA, 7 August 2008.
34. Younes A, Forero-Torres A, Bartlett NL et al. Objective responses in a Phase I dose-escalation study of SGN-35, a novel antibody-drug conjugate (ADC) targeting CD30, in patients with relapsed or refractory Hodgkin lymphoma. Am. Soc. Clin. Onc. Annu. Meet. Proc. 8526 (2008).
35. Harries M, Smith I. The development and clinical use of trastuzumab (Herceptin®). Endocr. Relat. Cancer. 9 (2), 75-85 (2002). (Pubitemid 34832161)
36. Lewis Phillips GD, Li G, Dugger DL et al. Targeting HER2-positive breast cancer with trastuzumab-DM1, an antibody-cytotoxic drug conjugate. Cancer Res. 68 (22), 9280-9290 (2008).
37. Krop I, LoRusso P, Miller KD et al. A Phase II study of trastuzumab-DM1 (T-DM1), a novel HER2 antibody-drug conjugate, in patients previously treated with lapatinib, trastuzumab, and chemotherapy. Presented at: The 33rd Annual CTRC-AACR San Antonio Breast Cancer Symposium. San Antonio, TX, USA, 12 December 2009. (Abstract 5090).
38. Wahl AF, Klussman K, Thompson JD et al. The anti-CD30 monoclonal antibody SGN-30 promotes growth arrest and DNA fragmentation in vitro and affects anti-tumor activity in models of Hodgkin's disease. Cancer Res. 62(13), 3736-3742 (2002). (Pubitemid 34728855)
39. + hematologic malignancies. Blood 111(4), 1848-1854 (2008). (Pubitemid 351451492)
40. Fanale M, Bartlett NL, Forero-Torres A et al. The antibody-drug conjugate brentuximab vedotin (SGN-35) induced multiple objective responses in patients with relapsed or refractory cd30-positive lymphomas in a Phase I weekly dosing study. Presented at: The 51st ASH Annual Meeting. New Orleans, LA, USA, 5-8 December 2009 (Abstract 2731).
41. Junttila TT, Li G, Parsons K et al. Trastuzumab-DM1 (T-DM1) retains all the mechanisms of action of trastuzumab and effciently inhibits growth of lapatinib insensitive breast cancer. Breast Cancer Res. Treat. DOI: 10.1007/s10549-010-1090-x (2010) (Epub ahead of print).
42. Sievers EL, Appelbaum FR, Spielberger RT et al. Selective ablation of acute myeloid leukemia using antibody-targeted chemotherapy: a Phase I study of an anti-CD33 calicheamicin immunoconjugate. Blood 93(11), 3678-3684 (1999). (Pubitemid 29249814)
43. + acute myeloid leukemia. Blood 106(4), 1183-1188 (2005). (Pubitemid 41129576)
44. Sievers EL, Larson RA, Stadtmauer EA et al. Effcacy and safety of gemtuzumab ozogamicin in patients with CD33-positive acute myeloid leukemia in frst relapse. J. Clin. Oncol. 19(13), 3244-3254 (2001). (Pubitemid 32591442)
45. Krop IE, Beeram M, Modi S et al. Phase I study of trastuzumab-DM1, an HER2 antibody-drug conjugate, given every 3 weeks to patients with HER2-positive metastatic breast cancer. J. Clin. Oncol. 28(16), 2698-2704 (2010).
46. Teicher BA. Antibody-drug conjugate targets. Curr. Cancer Drug Targets 9(8), 982-1004 (2009).
47. Jain RK. Normalization of tumor vasculature: an emerging concept in antiangiogenic therapy. Science 307(5706), 58-62 (2005). (Pubitemid 40093472)
48. Wu Y, Cain-Hom C, Choy L et al. Therapeutic antibody targeting of individual notch receptors. Nature 464(7291), 1052-1057 (2010).
49. Mukherjee S, Richardson AM, Rodriguez-Canales J et al. Identifcation of EpCAM as a molecular target of prostate cancer stroma. Am. J. Pathol. 175(6), 2277-2287 (2009).
50. Hofmeister V, Schrama D, Becker JC. Anti-cancer therapies targeting the tumor stroma. Cancer Immunol. Immunother. 57(1), 1-17 (2008). (Pubitemid 350043655)
51. Schliemann C, Neri D. Antibody-based vascular tumor targeting. Recent Results Cancer Res. 180, 201-216 (2010).
52. Minchinton AI, Tannock IF. Drug penetration in solid tumours. Nat. Rev. Cancer 6(8), 583-592 (2006). (Pubitemid 44140857)
53. Hanahan D, Weinberg RA. The hallmarks of cancer. Cell 100(1), 57-70 (2000). (Pubitemid 30046295)
54. Mahadevan D, Von Hoff DD. Tumor-stroma interactions in pancreatic ductal adenocarcinoma. Mol. Cancer Ther. 6(4), 1186-1197 (2007). (Pubitemid 46711982)
55. Vater CA, Manning C, Millar H et al. Anti-tumor effcacy of the integrin-targeted immunoconjugate IMGN388 in preclinical models. EORTC-NCI-AACR-2008. Molecular Targets and Cancer therapeutics. (2008) (Abstract #ENA-0399).
56. Thompson DS, Patnaik A, Bendell JC et al. A Phase I dose-escalation study of IMGN388 in patients with solid tumors. 28(15s) J. Clin. Oncol. (2010) (Abstract 3058).
57. Ostermann E, Garin-Chesa P, Heider KH et al. Effective immunoconjugate therapy in cancer models targeting a serine protease of tumor fbroblasts. Clin. Cancer Res. 14(14), 4584-4592 (2008).
58. Terrett JA, Devasthali V, Pan C et al. Ptk7 as a direct and tumor stroma target in multiple solid malignancies. Presented at: The 99th Annual Meeting of the American Association for Cancer Research. Philadelphia, PA, USA, 11-15 April 2008 (Abstract #1526).
59. Boman BM, Wicha MS. Cancer stem cells: a step toward the cure. J. Clin. Oncol. 26(17), 2795-2799 (2008).
60. Okamoto OK, Perez JF. Targeting cancer stem cells with monoclonal antibodies: a new perspective in cancer therapy and diagnosis. Expert. Rev. Mol. Diagn. 8(4), 387-393 (2008). (Pubitemid 351962085)
61. Clarke MF, Dick JE, Dirks PB et al. Cancer stem cells-perspectives on current status and future directions: AACR Workshop on cancer stem cells. Cancer Res. 66(19), 9339-9344 (2006). (Pubitemid 44623625)
62. Bonnet D, Dick JE. Human acute myeloid leukemia is organized as a hierarchy that originates from a primitive hematopoietic cell. Nat. Med. 3(7), 730-737 (1997). (Pubitemid 27298715)
63. Gil J, Stembalska A, Pesz KA et al. Cancer stem cells: the theory and perspectives in cancer therapy. J. Appl. Genet. 49(2), 193-199 (2008). (Pubitemid 351873043)
64. Jones RJ, Matsui WH, Smith BD. Cancer stem cells: are we missing the target? J. Natl Cancer Inst. 96(8), 583-585 (2004). (Pubitemid 38584981)
65. Bao S, Wu Q, McLendon RE et al. Glioma stem cells promote radioresistance by preferential activation of the DNA damage response. Nature 444(7120), 756-760 (2006). (Pubitemid 44949604)
66. Bao S, Wu Q, Sathornsumetee S et al. Stem cell-like glioma cells promote tumor angiogenesis through vascular endothelial growth factor. Cancer Res. 66(16), 7843-7848 (2006). (Pubitemid 44299144)
67. Dylla SJ, Beviglia L, Park IK et al. Colorectal cancer stem cells are enriched in xenogeneic tumors following chemotherapy. PLoS ONE 3(6), E2428 (2008).
68. Eyler CE, Rich JN. Survival of the fttest: cancer stem cells in therapeutic resistance and angiogenesis. J. Clin. Oncol. 26(17), 2839-2845 (2008).
69. Jin L, Hope KJ, Zhai Q et al. Targeting of CD44 eradicates human acute myeloid leukemic stem cells. Nat. Med. 12(10), 1167-1174 (2006). (Pubitemid 44527352)
70. Hosen N, Park CY, Tatsumi N et al. CD96 is a leukemic stem cell-specifc marker in human acute myeloid leukemia. Proc. Natl Acad. Sci. USA 104(26), 11008-11013 (2007). (Pubitemid 47175217)
71. Stabile H, Mitola S, Moroni E et al. Bone morphogenic protein antagonist Drm/gremlin is a novel proangiogenic factor. Blood 109(5), 1834-1840 (2007). (Pubitemid 46348177)
72. Sneddon JB, Zhen HH, Montgomery K et al. Bone morphogenetic protein antagonist gremlin 1 is widely expressed by cancer-associated stromal cells and can promote tumor cell proliferation. Proc. Natl Acad. Sci. USA 103(40), 14842-14847 (2006). (Pubitemid 44527816)
73. Piccirillo SG, Reynolds BA, Zanetti N et al. Bone morphogenetic proteins inhibit the tumorigenic potential of human brain tumour-initiating cells. Nature 444(7120), 761-765 (2006). (Pubitemid 44949605)
74. Namkoong H, Shin SM, Kim HK et al. The bone morphogenetic protein antagonist gremlin 1 is overexpressed in human cancers and interacts with YWHAH protein. BMC Cancer 6, 74 (2006).
75. Kohler G, Milstein C. Continuous cultures of fused cells secreting antibody of predefned specifcity. Nature 256(5517), 495-497 (1975).
76. Almagro JC, Fransson J. Humanization of antibodies. Front. Biosci. 13, 1619-1633 (2008). (Pubitemid 351611608)
77. Jones PT, Dear PH, Foote J et al. Replacing the complementarity- determining regions in a human antibody with those from a mouse. Nature 321 (6069), 522-525 (1986). (Pubitemid 16052256)
78. Roguska MA, Pedersen JT, Henry AH et al. A comparison of two murine monoclonal antibodies humanized by CDR-grafting and variable domain resurfacing. Protein Eng. 9(10), 895-904 (1996). (Pubitemid 26366515)
79. Roguska MA, Pedersen JT, Keddy CA et al. Humanization of murine monoclonal antibodies through variable domain resurfacing. Proc. Natl Acad. Sci. USA 91(3), 969-973 (1994). (Pubitemid 24048490)
80. Hwang WY, Foote J. Immunogenicity of engineered antibodies. Methods 36(1), 3-10 (2005). (Pubitemid 40558811)
81. Roopenian DC, Akilesh S. FcRn: the neonatal Fc receptor comes of age. Nat. Rev. Immunol. 7(9), 715-725 (2007). (Pubitemid 47327396)
82. Lonberg N. Human antibodies from transgenic animals. Nat. Biotechnol. 23(9), 1117-1125 (2005). (Pubitemid 41486393)
83. Lonberg N. Fully human antibodies from transgenic mouse and phage display platforms. Curr. Opin. Immunol. 20(4), 450-459 (2008).
84. Hoogenboom HR. Selecting and screening recombinant antibody libraries. Nat Biotechnol. 23(9), 1105-1116 (2005). (Pubitemid 41486392)
85. Kim SJ, Park Y, Hong HJ. Antibody engineering for the development of therapeutic antibodies. Mol. Cells 20(1), 17-29 (2005).
86. Carter PJ. Potent antibody therapeutics by design. Nat. Rev. Immunol. 6(5), 343-357 (2006).
87. Mascelli MA, Zhou H, Sweet R et al. Molecular, biologic, and pharmacokinetic properties of monoclonal antibodies: impact of these parameters on early clinical development. J. Clin. Pharmacol. 47(5), 553-565 (2007). (Pubitemid 46632148)
88. McDonagh CF, Kim KM, Turcott E et al. Engineered anti-CD70 antibody-drug conjugate with increased therapeutic index. Mol. Cancer Ther. 7(9), 2913-2923 (2008).
89. Strome SE, Sausville EA, Mann D. A mechanistic perspective of monoclonal antibodies in cancer therapy beyond target-related effects. Oncologist 12 (9), 1084-1095 (2007). (Pubitemid 350007020)
90. Fujimori K, Covell DG, Fletcher JE et al. A modeling analysis of monoclonal antibody percolation through tumors: a binding-site barrier. J. Nucl. Med. 31(7), 1191-1198 (1990). (Pubitemid 20213280)
91. Adams GP, Schier R, McCall AM et al. High affnity restricts the localization and tumor penetration of single-chain fv antibody molecules. Cancer Res. 61(12), 4750-4755 (2001). (Pubitemid 32691886)
92. Schmidt MM, Wittrup KD. A modeling analysis of the effects of molecular size and binding affnity on tumor targeting. Mol. Cancer Ther. 8(10), 2861-2871 (2009).
93. Jefferis R. Antibody therapeutics: isotype and glycoform selection. Expert Opin. Biol. Ther. 7(9), 1401-1413 (2007). (Pubitemid 47475656)
94. Salfeld JG. Isotype selection in antibody engineering. Nat. Biotechnol. 25(12), 1369-1372 (2007). (Pubitemid 350233124)
95. Stasi R. Gemtuzumab ozogamicin: an anti-CD33 immunoconjugate for the treatment of acute myeloid leukaemia. Expert Opin. Biol. Ther. 8(4), 527-540 (2008). (Pubitemid 351570415)
96. Hamann PR, Hinman LM, Hollander I et al. Gemtuzumab ozogamicin, a potent and selective anti-CD33 antibody-calicheamicin conjugate for treatment of acute myeloid leukemia. Bioconjug. Chem. 13(1), 47-58 (2002). (Pubitemid 34119634)
97. DiJoseph JF, Goad ME, Dougher MM et al. Potent and specifc antitumor effcacy of CMC-544, a CD22-targeted immunoconjugate of calicheamicin, against systemically disseminated B-cell lymphoma. Clin. Cancer Res. 10(24), 8620-8629 (2004). (Pubitemid 40053430)
98. DiJoseph JF, Armellino DC, Boghaert ER et al. Antibody-targeted chemotherapy with CMC-544: a CD22-targeted immunoconjugate of calicheamicin for the treatment of B-lymphoid malignancies. Blood 103(5), 1807-1814 (2004). (Pubitemid 38268977)
99. van der Neut Kolfschoten M, Schuurman J, Losen M et al. Anti-infammatory activity of human IgG4 antibodies by dynamic Fab arm exchange. Science 317(5844), 1554-1557 (2007). (Pubitemid 47417435)
100. Hamid O, Sznol M, Pavlick AC et al. Frequent dosing and GPNMB expression with CDX-011 (CR011-vcMMAE), an antibody-drug conjugate (ADC), in patients with advanced melanoma. J. Clin. Oncol. (Meeting Abstracts) 28(Suppl. 15), 8525 (2010).
101. Yoo EM, Wims LA, Chan LA et al. Human IgG2 can form covalent dimers. J. Immunol. 170(6), 3134-3138 (2003). (Pubitemid 36302189)
102. Ryan MC, Hering M, Peckham D et al. Antibody targeting of B-cell maturation antigen on malignant plasma cells. Mol. Cancer Ther. 6(11), 3009-3018 (2007). (Pubitemid 350206779)
103. Desjarlais JR, Lazar GA, Zhukovsky EA et al. Optimizing engagement of the immune system by anti-tumor antibodies: an engineer's perspective. Drug Discov. Today 12(21-22), 898-910 (2007). (Pubitemid 350052671)
104. Lazar GA, Dang W, Karki S et al. Engineered antibody Fc variants with enhanced effector function. Proc. Natl Acad. Sci. USA 103(11), 4005-4010 (2006).
105. Shields RL, Lai J, Keck R et al. Lack of fucose on human IgG1 N-linked oligosaccharide improves binding to human Fcgamma RIII and antibody-dependent cellular toxicity. J. Biol. Chem. 277(30), 26733-26740 (2002). (Pubitemid 34951677)
106. Shinkawa T, Nakamura K, Yamane N et al. The absence of fucose but not the presence of galactose or bisecting N-acetylglucosamine of human IgG1 complex-type oligosaccharides shows the critical role of enhancing antibody-dependent cellular cytotoxicity J. Biol. Chem. 278(5), 3466-3473 (2003). (Pubitemid 36801263)
107. Schuster M, Umana P, Ferrara C et al. Improved effector functions of a therapeutic monoclonal Lewis Y-specifc antibody by glycoform engineering. Cancer Res. 65(17), 7934-7941 (2005). (Pubitemid 41297272)
108. Lambert JM. Drug-conjugated monoclonal antibodies for the treatment of cancer. Curr. Opin. Pharmacol. 5(5), 543-549 (2005). (Pubitemid 41258574)
109. Chari RV. Targeted delivery of chemotherapeutics: tumor-activated prodrug therapy. Adv. Drug Deliv. Rev. 31(1-2), 89-104 (1998). (Pubitemid 28191877)
110. Chari RV, Martell BA, Gross JL et al. Immunoconjugates containing novel maytansinoids: promising anticancer drugs. Cancer Res. 52(1), 127-131 (1992).
111. Hinman LM, Hamann PR, Wallace R et al. Preparation and characterization of monoclonal antibody conjugates of the calicheamicins: a novel and potent family of anti-tumor antibiotics. Cancer Res. 53(14), 3336-3342 (1993). (Pubitemid 23223306)
112. Singh R, Erickson HK. Antibody-cytotoxic agent conjugates: preparation and characterization. In: Methods in Molecular Biology: Therapeutic Antibodies: Methods and Protocols 525, 445-467 (2008).
113. Baloglu E, Miller ML, Roller EE et al. Synthesis and biological evaluation of novel taxoids designed for targeted delivery to tumors. Bioorg. Med. Chem. Lett. 14(23), 5885-5888 (2004). (Pubitemid 39421538)
114. Miller ML, Roller EE, Wu X et al. Synthesis of potent taxoids for tumor-specifc delivery using monoclonal antibodies. Bioorg. Med. Chem. Lett. 14(15), 4079-4082 (2004). (Pubitemid 38844426)
115. Miller ML, Roller EE, Zhao RY et al. Synthesis of taxoids with improved cytotoxicity and solubility for use in tumor-specifc delivery. J. Med. Chem. 47(20), 4802-4805 (2004). (Pubitemid 39238252)
116. Ojima I, Geng X, Wu X et al. Tumor-specifc novel taxoid-monoclonal antibody conjugates. J. Med. Chem. 45(26), 5620-5623 (2002). (Pubitemid 35453753)
117. Burke PJ, Senter PD, Meyer DW et al. Design, synthesis, and biological evaluation of antibody-drug conjugates comprised of potent camptothecin analogues. Bioconjug. Chem. 20(6), 1242-1250 (2009).
118. Burke PJ, Toki BE, Meyer DW et al. Novel immunoconjugates comprised of streptonigrin and 17-amino-geldanamycin attached via a dipeptide-p-aminobenzyl- amine linker system. Bioorg. Med. Chem. Lett. 19(10), 2650-2653 (2009).
119. Bross PF, Beitz J, Chen G et al. Approval summary: gemtuzumab ozogamicin in relapsed acute myeloid leukemia. Clin. Cancer Res. 7(6), 1490-1496 (2001). (Pubitemid 32708610)
120. Zein N, Sinha AM, McGahren WJ et al. Calicheamicin γ 1I: an antitumor antibiotic that cleaves double-stranded DNA site specifcally Science 240(4856), 1198-1201 (1988).
121. DiJoseph JF, Dougher MM, Kalyandrug LB et al. Antitumor effcacy of a combination of CMC-544 (inotuzumab ozogamicin), a CD22-targeted cytotoxic immunoconjugate of calicheamicin, and rituximab against non-Hodgkin's B-cell lymphoma. Clin. Cancer. Res. 12(1), 242-249 (2006). (Pubitemid 43166200)
122. DiJoseph JF, Khandke K, Dougher MM et al. CMC-544 (inotuzumab ozogamicin): a CD22-targeted immunoconjugate of calicheamicin. Hematology Meeting Reports 5(6), 74-77 (2008).
123. DiJoseph JF, Dougher MM, Armellino DC et al. CD20-specifc antibody-targeted chemotherapy of non-Hodgkin's B-cell lymphoma using calicheamicin-conjugated rituximab. Cancer Immunol. Immunother. 56(7), 1107-1117 (2007). (Pubitemid 46675304)
124. Boghaert ER, Sridharan L, Khandke KM et al. The oncofetal protein, 5T4, is a suitable target for antibody-guided anticancer chemotherapy with calicheamicin. Int. J. Oncol. 32 (1), 221-234 (2008). (Pubitemid 351176081)
125. Hamann PR, Hinman LM, Beyer CF et al. A calicheamicin conjugate with a fully humanized anti-MUC1 antibody shows potent antitumor effects in breast and ovarian tumor xenografts. Bioconjug. Chem. 16(2), 354-360 (2005). (Pubitemid 40388211)
126. MacMillan KS, Boger DL. Fundamental relationships between structure, reactivity and biological activity for the duocarmycins and CC-1065. J. Med. Chem. 52(19), 5771-5780 (2009).
127. Chari RV, Jackel KA, Bourret LA et al. Enhancement of the selectivity and antitumor effcacy of a CC-1065 analogue through immunoconjugate formation. Cancer Res. 55(18), 4079-4084 (1995).
128. Tietze LF, Krewer B. Antibody-directed enzyme prodrug therapy: a promising approach for a selective treatment of cancer based on prodrugs and monoclonal antibodies. Chem. Biol. Drug Des. 74(3), 205-211 (2009).
129. Tietze LF, Krewer B. Novel analogues of CC-1065 and the duocarmycins for the use in targeted tumour therapies. Anticancer Agents Med. Chem. 9(3), 304-325 (2009).
130. Tietze LF, Panknin O, Krewer B et al. Synthesis and biological evaluation of a novel pentagastrin-toxin conjugate designed for a targeted prodrug monotherapy of cancer. Int. J. Mol. Sci. 9(5), 821-837 (2008). (Pubitemid 351776198)
131. King D, Terrett J, Cardarelli P et al. Mechanism of activation of a human anti-cd70 antibody-mgba conjugate and effcacy in a nude rat model of renal carcinoma. AACR Meeting Abstracts (1 Annual Meeting 2008). 4057 (2008).
132. Cardarelli P, King D, Terrett J et al. Effcacy and safety of a human anti-CD70 antibody-MGBA conjugate. AACR Meeting Abstracts (1 Annual Meeting 2008). 4061 (2008).
133. Widdison WC, Wilhelm SD, Cavanagh EE et al. Semisynthetic maytansine analogues for the targeted treatment of cancer. J. Med. Chem. 49(14), 4392-4408 (2006). (Pubitemid 44036683)
134. Lopus M, Oroudjev E, Wilson L et al. Maytansine derivatives and metabolites of antibody-maytansinoid conjugates inhibit microtubule polymerization and strongly suppress microtubule dynamics. AACR Meeting Abstracts (1 Annual Meeting 2008). 1406 (2008).
135. Oroudjev E, Lopus M, Wilson L et al. Antibody-maytansinoid conjugates affect microtubule morphology and suppress microtubule dynamics in live cells. AACR Meeting Abstracts (1 Annual Meeting 2008). 1403 (2008).
136. Remillard S, Rebhun LI, Howie GA et al. Antimitotic activity of the potent tumor inhibitor maytansine. Science 189(4207), 1002-1005 (1975).
137. Drewinko B, Patchen M, Yang LY et al. Differential killing effcacy of twenty anti-tumor drugs on proliferating and nonproliferating human tumor cells. Cancer Res. 41(6), 2328-2333 (1981). (Pubitemid 11111437)
138. Murphy M, Phinney S, Ab O et al. Immunohistochemical analysis of the glycotope targeted by huC242-DM4 indicates strong expression in several tumor types with unmet medical need. AACR Meeting Abstracts (1 Annual Meeting 2008). 4898 (2008).
139. Tolcher AW, Ochoa L, Hammond LA et al. Cantuzumab mertansine, a maytansinoid immunoconjugate directed to the CanAg antigen: a Phase I, pharmacokinetic, and biologic correlative study. J. Clin. Oncol. 21(2), 211-222 (2003). (Pubitemid 46606149)
140. Baeckstrom D, Hansson GC, Nilsson O et al. Purifcation and characterization of a membrane-bound and a secreted mucin-type glycoprotein carrying the carcinoma-associated sialyl-Lea epitope on distinct core proteins. J. Biol. Chem. 266(32), 21537-21547 (1991). (Pubitemid 121000217)
141. Helft PR, Schilsky RL, Hoke FJ et al. A Phase I study of cantuzumab mertansine administered as a single intravenous infusion once weekly in patients with advanced solid tumors. Clin. Cancer Res. 10(13), 4363-4368 (2004). (Pubitemid 38878875)
142. Polson AG, Yu SF, Elkins K et al. Antibody-drug conjugates targeted to CD79 for the treatment of non-Hodgkin lymphoma. Blood 110(2), 616-623 (2007). (Pubitemid 47105400)
143. Stephan JP, Chan P, Lee C et al. Anti-CD22-MCC-DM1 and MC-MMAF conjugates: impact of assay format on pharmacokinetic parameters determination. Bioconjug. Chem. 19(8), 1673-1683 (2008).
144. Mayo MF LA, Wang L, Wunderli P, Payne G, Xie H, Lutz RJ. In vivo stability in mice of SAR566658 (huDS6-DM4), an immunoconjugate targeting solid tumors. EORTC-NCI-AACR Proceedings (2008) (Abstract 533).
145. Carrigan C, Zuany-Amorim C, Mayo MF et al. Preclinical evaluation of SAR566658 (huDS6-DM4) in mice bearing human tumor xenografts of breast, ovarian, lung, cervical and pancreatic cancer. EORTC Meeting Abstracts Annual Meeting (2008) (Abstract 525).
146. Bai R, Pettit GR, Hamel E. Dolastatin 10, a powerful cytostatic peptide derived from a marine animal. Inhibition of tubulin polymerization mediated through the vinca alkaloid binding domain. Biochem. Pharmacol. 39(12), 1941-1949 (1990). (Pubitemid 20187330)
147. Doronina SO, Toki BE, Torgov MY et al. Development of potent monoclonal antibody auristatin conjugates for cancer therapy. Nat. Biotechnol. 21(7), 778-784 (2003). (Pubitemid 36791396)
148. Doronina SO, Mendelsohn BA, Bovee TD et al. Enhanced activity of monomethylauristatin F through monoclonal antibody delivery: effects of linker technology on effcacy and toxicity Bioconjug Chem. 17(1), 114-124 (2006). (Pubitemid 43157592)
149. Gerber H-P, Kung-Sutherland M, Stone I et al. Potent anti-tumor activity of the anti-CD19 auristatin antibody-drug conjugate SGN-19A in rituximab sensitive and resistant lymphomas. EORTC Meeting Abstracts (2008) (Abstract 507).
150. Gerber HP, Kung-Sutherland M, Stone I et al. Potent antitumor activity of the anti-CD19 auristatin antibody drug conjugate hBU12-vcMMAE against rituximab-sensitive and-resistant lymphomas. Blood 113(18), 4352-4361 (2009).
151. Dornan D, Bennett F, Chen Y et al. Therapeutic potential of an anti-CD79b antibody-drug conjugate, anti-CD79b-vcMMAE, for the treatment of non-Hodgkin lymphoma. Blood 114(13), 2721-2729 (2009).
152. Jackson D, Gooya J, Mao S et al. A human antibody-drug conjugate targeting EphA2 inhibits tumor growth in vivo. Cancer Res. 68(22), 9367-9374 (2008).
153. Lee JW, Han HD, Shahzad MM et al. EphA2 immunoconjugate as molecularly targeted chemotherapy for ovarian carcinoma. J. Natl Cancer Inst. 101(17), 1193-1205 (2009).
154. Alley SC, Benjamin DR, Jeffrey SC et al. Contribution of linker stability to the activities of anticancer immunoconjugates. Bioconjug Chem. 19(3),
155. Doronina SO, Bovee TD, Meyer DW et al. Novel peptide linkers for highly potent antibody-auristatin conjugate. Bioconjug. Chem. 19(10), 1960-1963 (2008).
156. Wang L, Amphlett G, Blattler WA et al. Structural characterization of the maytansinoid-monoclonal antibody immunoconjugate, huN901-DM1, by mass spectrometry. Protein Sci. 14(9), 2436-2446 (2005). (Pubitemid 41252812)
157. Junutula JR, Raab H, Clark S et al. Site-specifc conjugation of a cytotoxic drug to an antibody improves the therapeutic index. Nat. Biotechnol. 26(8), 925-932 (2008).
158. 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. 10(20), 7063-7070 (2004). (Pubitemid 39383058)
159. McDonagh CF, Turcott E, Westendorf L et al. Engineered antibody-drug conjugates with defned sites and stoichiometries of drug attachment. Protein Eng. Des. Sel. 19(7), 299-307 (2006). (Pubitemid 43999640)
160. Wu G, Fang YZ, Yang S et al. Glutathione metabolism and its implications for health. J. Nutr. 134(3), 489-492 (2004). (Pubitemid 38298485)
161. Mills BJ, Lang CA. Differential distribution of free and bound glutathione and cyst(e)ine in human blood. Biochem. Pharmacol. 52(3), 401-406 (1996). (Pubitemid 26233582)
162. Appenzeller-Herzog C, Ellgaard L. The human PDI family: versatility packed into a single fold. Biochim. Biophys. Acta 1783(4), 535-548 (2008).
163. Ciechanover A. Intracellular protein degradation: from a vague idea thru the lysosome and the ubiquitin-proteasome system and onto human diseases and drug targeting. Hematology Am. Soc. Hematol. Educ. Program 1-12, 505-506 (2006).
164. Hamann PR, Hinman LM, Beyer CF et al. An anti-CD33 antibody-calicheamicin conjugate for treatment of acute myeloid leukemia. Choice of linker. Bioconjug. Chem. 13(1), 40-46 (2002). (Pubitemid 34119633)
165. Boghaert ER, Khandke KM, Sridharan L et al. Determination of pharmacokinetic values of calicheamicin-antibody conjugates in mice by plasmon resonance analysis of small (5 microl) blood samples. Cancer Chemother. Pharmacol. 61(6), 1027-1035 (2008). (Pubitemid 351423131)
166. Dowell JA, Korth-Bradley J, Liu H et al. Pharmacokinetics of gemtuzumab ozogamicin, an antibody-targeted chemotherapy agent for the treatment of patients with acute myeloid leukemia in frst relapse. J. Clin. Pharmacol. 41(11), 1206-1214 (2001). (Pubitemid 32983219)
167. Kovtun YV, Audette CA, Mayo MF et al. Antibody-maytansinoid conjugates designed to bypass multidrug resistance. Cancer Res. 70(6), 2528-2537 (2010).
168. Lutz RJ, Xie H, Widdison WC et al. HuC242-DM4, an antibody-maytansinoid conjugate with superior preclinical activity in human CanAg-positive tumor xenograft models in SCID mice. AACR Meeting Abstracts 2005(1), 334-335 (2005).
169. 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. 66(8), 4426-4433 (2006).
170. Erickson H, Wilhelm S, Widdison W et al. Evaluation of the cytotoxic potencies of the major maytansinoid metabolites of antibody-maytansinoid conjugates detected in vitro and in preclinical mouse models. AACR Meeting Abstracts 2008 (Annual Meeting), 2150 (2008).
171. Francisco JA, Cerveny CG, Meyer DL et al. cAC10-vcMMAE, an anti-CD30-monomethyl auristatin E conjugate with potent and selective antitumor activity. Blood 102(4), 1458-1465 (2003). (Pubitemid 36988057)
172. Okeley NM, Miyamoto JB, Zhang X et al. Intracellular activation of SGN-35, a potent anti-CD30 antibody-drug conjugate. Clin. Cancer Res. 16(3), 888-897 (2010).
173. Sanderson RJ, Hering MA, James SF et al. In vivo drug-linker stability of an anti-CD30 dipeptide-linked auristatin immunoconjugate. Clin. Cancer Res. 11(2 Part 1), 843-852 (2005). (Pubitemid 40116913)
174. Walter RB, Raden BW, Hong TC et al. Multidrug resistance protein attenuates gemtuzumab ozogamicin-induced cytotoxicity in acute myeloid leukemia cells. Blood 102(4), 1466-1473 (2003). (Pubitemid 36988058)
175. Linenberger ML, Hong T, Flowers D et al. Multidrug-resistance phenotype and clinical responses to gemtuzumab ozogamicin. Blood 98(4), 988-994 (2001).
176. Leonard GD, Fojo T, Bates SE. The role of ABC transporters in clinical practice. Oncologist 8(5), 411-424 (2003). (Pubitemid 37238869)
177. Gottesman MM, Pastan I. The multidrug transporter, a double-edged sword. J. Biol. Chem. 263(25), 12163-12166 (1988).
178. Takara K, Sakaeda T, Okumura K. An update on overcoming MDR1-mediated multidrug resistance in cancer chemotherapy. Curr. Pharm. Des. 12(3), 273-286 (2006).
179. Hamann PR, Hinman LM, Beyer CF et al. An anti-MUC1 antibody-calicheamicin conjugate for treatment of solid tumors. Choice of linker and overcoming drug resistance. Bioconjug. Chem. 16(2), 346-353 (2005). (Pubitemid 40388210)
180. Guillemard V, Uri Saragovi H. Prodrug chemotherapeutics bypass P-glycoprotein resistance and kill tumors in vivo with high effcacy and target-dependent selectivity Oncogene 23(20), 3613-3621 (2004). (Pubitemid 38658428)
181. Kovtun Y AC, Maloney E, Mayo M et al. Novel antibody-maytansinoid conjugates with improved effcacy against multidrug-resistant tumors. EORTC Proceedings (2008) (Abstract 518).
182. DiJoseph JF, Dougher MM, Armellino DC et al. Therapeutic potential of CD22-specifc antibody-targeted chemotherapy using inotuzumab ozogamicin (CMC-544) for the treatment of acute lymphoblastic leukemia. Leukemia 21(11), 2240-2245 (2007). (Pubitemid 350011695)
183. Roepstorff K, Grovdal L, Grandal M et al. Endocytic downregulation of ErbB receptors: mechanisms and relevance in cancer. Histochem. Cell. Biol. 129(5), 563-578 (2008).
184. + multiple myeloma cells. Cancer Res. 64(13), 4629-4636 (2004). (Pubitemid 38856937)
185. Jensen M, Berthold F. Targeting the neural cell adhesion molecule in cancer. Cancer Lett. 258(1), 9-21 (2007). (Pubitemid 47600500)
186. Whiteman KR, Murphy M.F, Cohane KP et al. Preclinical evaluation of IMGN901 (huN901-DM1) as a potential therapeutic for ovarian cancer. Am. Assoc. Clin. Res. Annu. Meet. (2008) (Abstract 2135).
187. Roy DC, Ouellet S, Le Houillier C et al. Elimination of neuroblastoma and small-cell lung cancer cells with an antineural cell adhesion molecule immunotoxin. J. Natl. Cancer Inst. 88(16), 1136-1145 (1996). (Pubitemid 26276310)
188. + solid tumors: results from a Phase I/II trial (study 001) and a Phase I trial (study 002). Presented at: The 13th World Conference on Lung Cancer. San Francisco, CA, USA, 31 July-4 August 2009.
189. Woll PJ, Lorigan P, O'Brien M et al. Clinical experience of IMGN901 (BB-10901, huN901-DM1) in patients with Merkel-cell carcinoma (MCC). AACR-NCI-EORTC (2009) (Abstract B237).
190. Thompson D, Patnaik A, Bendell J et al. A Phase I dose-escalation study of IMGN388 in patients with solid tumors. J. Clin. Oncol. 28(15s) (2010) (Abstract 3058).
191. Aboukameel A, Goustin A-S, Mohammad R et al. Superior anti-tumor activity of the CD19-directed immunotoxin, SAR3419 to rituximab in non-Hodgkin's xenograft animal models: preclinical evaluation. ASH Annual Meeting Abstracts 110, (2007) (Abstract 2339).
192. Ikeda H, Hideshima T, Lutz RJ et al. The monoclonal antibody nBT062 conjugated to cytotoxic maytansinoids has potent and selective cytotoxicity against cd138 positive multiple myeloma cells in vitro and in vivo. ASH Annual Meeting Abstracts. 112(11), 1716 (2008).
193. Chanan-Khan AA, Jagannath S, Heffner LT et al. Phase I study of BT062 given as repeated single dose once every 3 weeks in patients with relapsed or relapsed/refractory multiple myeloma. ASH Annual Meeting Abstracts 114(22), 1862 (2009).
194. Ofazoglu E, Kissler KM, Sievers EL et al. Combination of the anti-CD30-auristatin-E antibody-drug conjugate (SGN-35) with chemotherapy improves antitumour activity in Hodgkin lymphoma. Br. J. Haematol. 142(1), 69-73 (2008). (Pubitemid 351783148)
195. Hwu P, Sznol M., Pavlick A. et al. A Phase I/II study of CRO-11-vcMMAE, an antibody-drug conjugate, in patients with unresectable stage III or stage IV melanoma. Am. Soc. Clin. Onc. Annu. Meet. Proc. 9029 (2008).
196. Sznol M, Hamid O, Hwu P et al. Pharmacokinetics (PK) of CR011-vcMMAE, an antibody-drug conjugate (ADC), in a Phase (Ph) I study of patients (pts) with advanced melanoma. J. Clin. Oncol. (Meeting Abstracts) 27(15S), 9063 (2009).
197. Tse KF, Jeffers M, Pollack VA et al. CR011, a fully human monoclonal antibody-auristatin E conjugate, for the treatment of melanoma. Clin. Cancer Res. 12(4), 1373-1382 (2006). (Pubitemid 43342531)
198. Kantoff P, Petrylak DP, Pomerantz M et al. First-in-human Phase I trial of prostate-specifc membrane antigen antibody drug conjugate (PSMA ADC) in taxane-refractory prostate cancer. J. Clin. Oncol. 28(15S), TPS245 (2010).
199. Tolcher AW, Forouzesh B, McCreery H et al. A Phase I and pharmacokinetic study of BB-10901, a maytansinoid immunoconjugate, in CD56-expressing tumors. Presented at: The EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics (2005).
200. Chanan-Khan AA, Jagannath S, Munshi NC et al. Phase I study of huN901-DM1 (BB-10901) in patients with relapsed and relapsed/refractory CD56-positive multiple myeloma. ASH Annual Meeting Abstracts, Part 1. 110, 1174 (2007).
201. McCann J, Fossella FV, Villalona-Calero MA et al. Phase II trial of huN901-DM1 in patients with relapsed small cell lung cancer (SCLC) and CD56-positive small-cell carcinoma. Am. Soc. Clin. Onc. Annu. Meet. Proc. 25, 18084 (2007).
202. Giles F Morariu-Zamfr R, Lambert JM, Verstovsek S et al. Phase I study of AVE9633, an anti-CD33-maytansinoid immunoconjugate, administered as an intravenous infusion in patients with refractory/relapsed CD33-positive acute myeloid leukemia (AML). Am. Soc. Hematol. Annu. Meet. Proc. (2006).
203. Larson RA, Sievers EL, Stadtmauer EA et al. Final report of the effcacy and safety of gemtuzumab ozogamicin (Mylotarg®) in patients with CD33-positive acute myeloid leukemia in frst recurrence. Cancer 104(7), 1442-1452 (2005). (Pubitemid 41356159)
204. Giles FJ. Gemtuzumab ozogamicin: promise and challenge in patients with acute myeloid leukemia. Expert Rev. Anticancer Ther. 2(6), 630-640 (2002). (Pubitemid 35469485)
205. Sauter A, Kloft C, Gronau S et al. Pharmacokinetics, immunogenicity and safety of bivatuzumab mertansine, a novel CD44v6-targeting immunoconjugate, in patients with squamous cell carcinoma of the head and neck. Int. J. Oncol. 30(4), 927-935 (2007).
206. Rupp U, Schoendorf-Holland E, Eichbaum M et al. Safety and pharmacokinetics of bivatuzumab mertansine in patients with CD44v6-positive metastatic breast cancer: fnal results of a Phase I study. Anticancer Drugs 18(4), 477-485 (2007). (Pubitemid 46712412)
207. Tijink BM, Buter J, de Bree R et al. A Phase I dose escalation study with anti-CD44v6 bivatuzumab mertansine in patients with incurable squamous cell carcinoma of the head and neck or esophagus. Clin. Cancer Res. 12(20 Part 1), 6064-6072 (2006). (Pubitemid 44703770)
208. Riechelmann H, Sauter A, Golze W et al. Phase I trial with the CD44v6-targeting immunoconjugate bivatuzumab mertansine in head and neck squamous cell carcinoma. Oral Oncol. 44(9), 823-829 (2008).
209. Heider KH, Mulder JWR, Ostermann E et al. Splice variants of the cell surface glycoprotein CD44 associated with metastatic tumour cells are expressed in normal tissues of humans and cynomolgus monkeys. Eur. J. Cancer 31(13-14), 2385 (1995).
210. van der Velden VH, Boeckx N, Jedema I et al. High CD33-antigen loads in peripheral blood limit the effcacy of gemtuzumab ozogamicin (Mylotarg®) treatment in acute myeloid leukemia patients. Leukemia 18(5), 983-988 (2004). (Pubitemid 38714624)
211. Davies Q, Perkins AC, Frier M et al. The effect of circulating antigen on the biodistribution of the engineered human antibody hCTM01 in a nude mice model. Eur. J. Nucl. Med. 24(2), 206-209 (1997). (Pubitemid 27121102)
212. Baselga J, Tripathy D, Mendelsohn J et al. Phase II study of weekly intravenous recombinant humanized anti-p185HER2 monoclonal antibody in patients with HER2/neu-overexpressing metastatic breast cancer. J. Clin. Oncol. 14(3), 737-744 (1996).
213. Pegram MD, Lipton A, Hayes DF et al. Phase II study of receptor-enhanced chemosensitivity using recombinant humanized anti-p185HER2/neu monoclonal antibody plus cisplatin in patients with HER2/neu-overexpressing metastatic breast cancer refractory to chemotherapy treatment. J. Clin. Oncol. 16(8), 2659-2671 (1998). (Pubitemid 28363029)
214. Qin AW, Watermill J, Mastico RA et al. The pharmacokinetics and pharmacoldynamics of IMGN242 (huC242-DM4) in patients with CanAg-expressing solid tumors. Am. Soc. Clin. Onc. Annu. Meet. Proc. 3066 (2008).