Antibody-drug conjugate (ADC) clinical pipeline: A review

Methods in Molecular Biology

Volumn 1045, Issue , 2013, Pages 1-27

  Sassoon, Ingrid ^a   Blanc, Véronique ^a  

^a SANOFI   (France)

Author keywords

Antibody; Antibody drug conjugate; Auristatin; Calicheamicin; Cancer; CMC 544; Cytotoxic; Linker; Maytansine; SGN 35; T DM1

Indexed keywords

AGS 16M 8F; AGS 22M 6E; AGS 5M 2E; AGS 6MF; AMG 172; AMG 595; ANTIBODY CONJUGATE; ANTIBODY DRUG CONJUGATE; ANTINEOPLASTIC AGENT; ASG 22ME; ASG 5ME; AVE 9633; BAY 79 4620; BAY 94 9343; BIIB 015; BRENTUXIMAB VEDOTIN; BT 062; CANTUZUMAB RAVTANSINE; CMB 401; CMD 193; DCDS 4501A; DCDT 2980S; DEDN 6526A; DOXORUBICIN; DRUG ANTIBODY; DSTP 3086S; GEMTUZUMAB OZOGAMICIN; GLEMBATUMUMAB VEDOTIN; HUDS 6DM 4; IMGN 388; IMGN 529; IMMU 110; IMMU 130; INOTUZUMAB OZOGAMICIN; LORVOTUZUMAB MERTANSINE; MDX 1203; MEDI 547; MILATUZUMAB; MLN 2704; MONOCLONAL ANTIBODY; PSMA ADC; PSMA ADC 1301; RG 7450; RG 7458; RG 7593; RG 7596; RG 7598; RG 7599; RG 7600; SAR 3419; SAR 566658; SGN 15; TRASTUZUMAB EMTANSINE; UNCLASSIFIED DRUG;

ACUTE LYMPHOBLASTIC LEUKEMIA; BACKACHE; BETA CELL NONHODGKIN LYMPHOMA; BIOLOGICAL THERAPY; BLOOD TOXICITY; BLURRED VISION; BREAST CANCER; BREAST METASTASIS; CANCER PATIENT; CANCER THERAPY; CLINICAL TRIAL (TOPIC); COLORECTAL CANCER; CONJUGATE; DESQUAMATION; DRUG DOSE ESCALATION; EYE TOXICITY; FATIGUE; GLIOMA; HAND FOOT SYNDROME; HEADACHE; HEMATOLOGIC MALIGNANCY; HODGKIN DISEASE; HUMAN; KIDNEY CANCER; KIDNEY CARCINOMA; LARGE CELL LYMPHOMA; LEARNING CURVE; LUNG CANCER; LUNG SMALL CELL CANCER; MELANOMA; MERKEL CELL TUMOR; MUCOSA INFLAMMATION; MULTIPLE MYELOMA; MYALGIA; NEUROPATHY; NEUTROPENIA; NONHODGKIN LYMPHOMA; NONHUMAN; PANCREAS CANCER; PATIENT SELECTION; PHASE 3 CLINICAL TRIAL (TOPIC); PRIORITY JOURNAL; PROSTATE CANCER; RASH; REVIEW; SHOULDER PAIN; SOLID TUMOR; STOMACH CANCER; THROMBOCYTOPENIA;

EID: 84934444640     PISSN: 10643745     EISSN: None     Source Type: Book Series    
DOI: 10.1007/978-1-62703-541-5_1     Document Type: Review

References (125)

1. Reichert JM (2012) Marketed therapeutic antibodies compendium. MAbs 4:413-415
2. Larson RA, Sievers EL, Stadtmauer EA et al (2005) Final report of the efficacy and safety of gemtuzumab ozogamicin (Mylotarg) in patients with CD33-positive acute myeloid leukemia in first recurrence. Cancer 104:1442-1452
3. Sievers EL, Larson RA, Stadtmauer EA et al (2001) Efficacy and safety of gemtuzumab ozogamicin in patients with CD33-positive acute myeloid leukemia in first relapse. J Clin Oncol J Am Soc Clin Oncol 19:3244-3254
4. Ricart AD (2011) Antibody-drug conjugates of calicheamicin derivative: Gemtuzumab ozogamicin and inotuzumab ozogamicin. Clin Cancer Res J Am Assoc Cancer Res 17:6417-6427
5. Teicher BA (2009) Antibody-drug conjugate targets. Curr Cancer Drug Targets 9:982-1004
6. Helft PR, Schilsky RL, Hoke FJ et al (2004) A phase I study of cantuzumab mertansine administered as a single intravenous infusion once weekly in patients with advanced solid tumors. Clin Cancer Res J Am Assoc Cancer Res 10:4363-4368
7. Tolcher AW, Ochoa L, Hammond LA et al (2003) Cantuzumab mertansine, a maytansinoid immunoconjugate directed to the CanAg antigen: A phase I, pharmacokinetic, and biologic correlative study. J Clin Oncol J Am Soc Clin Oncol 21:211-222
8. Heider K, Kuthan H, Stehle G et al (2004) CD44v6: A target for antibody-based cancer therapy. Cancer Immunol Immunother CII 53:567-579
9. Riechelmann H, Sauter A, Golze W et al (2008) Phase I trial with the CD44v6-targeting immunoconjugate bivatuzumab mertansine in head and neck squamous cell carcinoma. Oral Oncol 44:823-829
10. Sauter A, Kloft C, Gronau S et al (2007) 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 30:927-935
11. Tijink BM, Buter J, Bree R et al (2006) 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 J Am Assoc Cancer Res 12:6064-6072
12. Lapusan S, Vidriales MB, Thomas X et al (2012) Phase I studies of AVE9633, an anti-CD33 antibody-maytansinoid conjugate, in adult patients with relapsed/refractory acute myeloid leukemia. Invest New Drugs 30:1121-1131
13. Chari R, Xie H, Leece B (2005) Preclinical evaluationof ananti-CD33-maytansinoidimmunoconjugate, huMy9-6-DM4 (AVE9633) for the targeted therapy of acute myeloid leukemia.Am Assoc Cancer Res, Abstract LB-287
14. Chari RV (2008) Targeted cancer therapy: Conferring specificity to cytotoxic drugs. Acc Chem Res 41:98-107
15. Kratz F, Ajaj KA, Warnecke A (2007) Anticancer carrier-linked prodrugs in clinical trials. Expert Opin Investig Drugs 16:1037-1058
16. Senter PD (2009) Potent antibody drug conjugates for cancer therapy. Curr Opin Chem Biol 13:235-244
17. Chari RV, Martell BA, Gross JL et al (1992) Immunoconjugates containing novel maytansinoids: Promising anticancer drugs. Cancer Res 52:127-131
18. Widdison WC, Wilhelm SD, Cavanagh EE et al (2006) Semisynthetic maytansine analogues for the targeted treatment of cancer. J Med Chem 49:4392-4408
19. Doronina SO, Mendelsohn BA, Bovee TD et al (2006) Enhanced activity of monomethylauristatin F through monoclonal antibody delivery: Effects of linker technology on efficacy and toxicity. Bioconjug Chem 17:114-124
20. Hamann PR, Hinman LM, Beyer CF et al (2002) An anti-CD33 antibody-calicheamicin conjugate for treatment of acute myeloid leukemia. Choice of linker. Bioconjug Chem 13:40-46
21. Tietze LF, Krewer B (2009) Novel analogues of CC-1065 and the duocarmycins for the use in targeted tumour therapies. Anticancer Agent Med Chem 9:304-325
22. Ducry L, Stump B (2010) Antibody-drug conjugates: Linking cytotoxic payloads to monoclonal antibodies. Bioconjug Chem 21:5-13
23. Erickson HK, Park PU, Widdison WC, Kovtun YV, Garrett LM, Hoffman K, Lutz RJ, Goldmacher VS, Blattler WA (2006) Antibody-maytansinoid conjugates are activated in targeted cancer cells by lysosomal degradation and linker-dependent intracellular processing. Cancer Res 66:4426-4433
24. Doronina SO, Toki BE, Torgov MY et al (2003) Development of potent monoclonal antibody auristatin conjugates for cancer therapy. Nat Biotechnol 21:778-784
25. Erickson HK, Widdison WC, Mayo MF et al (2010) Tumor delivery and in vivo processing of disulfide-linked and thioether-linked antibody-maytansinoid conjugates. Bioconjug Chem 21:84-92
26. Kellogg BA, Garrett L, Kovtun Y et al (2011) Disulfide-linked antibody-maytansinoid conjugates: Optimization of in vivo activity by varying the steric hindrance at carbon atoms adjacent to the disulfide linkage. Bioconjug Chem 22:717-727
27. Okeley NM, Miyamoto JB, Zhang X et al (2010) Intracellular activation of SGN-35, a potent anti-CD30 antibody-drug conjugate. Clin Cancer Res J Am Assoc Cancer Res 16:888-897
28. Kovtun YV, Audette CA, Ye Y et al (2006) Antibody-drug conjugates designed to eradicate tumors with homogeneous and heterogeneous expression of the target antigen. Cancer Res 66:3214-3221
29. Sanderson RJ, Hering MA, James SF et al (2005) In vivo drug-linker stability of an anti-CD30 dipeptide-linked auristatin immunoconjugate. Clin Cancer Res J Am Assoc Cancer Res 11:843-852
30. Hamblett KJ, Senter PD, Chace DF et al (2004) Effects of drug loading on the antitumor activity of a monoclonal antibody drug conjugate. Clin Cancer Res J Am Assoc Cancer Res 10:7063-7070
31. Shen B, Xu K, Liu L et al (2012) Conjugation site modulates the in vivo stability and therapeutic activity of antibody-drug conjugates. Nat Biotechnol 30:184-189
32. Wakankar A, Chen Y, Gokarn Y et al (2011) Analytical methods for physicochemical characterization of antibody drug conjugates. MAbs 3:161-172
33. Deutsch YE, Tadmor T, Podack ER et al (2011) CD30: An important new target in hematologic malignancies. Leuk Lymphoma 52:1641-1654
34. Gerber H (2010) Emerging immunotherapies targeting CD30 in Hodgkin's lymphoma. Biochem Pharmacol 79:1544-1552
35. Katz J, Janik JE, Younes A (2011) Brentuximab vedotin (SGN-35). Clin Cancer Res J Am Assoc Cancer Res 17:6428-6436
36. Younes A (2011) CD30-targeted antibody therapy. Curr Opin Oncol 23:587-593
37. Furtado M, Rule S (2012) Emerging pharmacotherapy for relapsed or refractory Hodgkin's lymphoma: Focus on brentuximab vedotin. Clin Med Insight Oncol 6:31-39
38. Pro B, Advani R, Brice P et al (2012) Brentuximab vedotin (SGN-35) in patients with relapsed or refractory systemic anaplastic large-cell lymphoma: Results of a phase II study. J Clin Oncol J Am Soc Clin Oncol 30:2190-2196
39. Senter PD, Sievers EL (2012) The discovery and development of brentuximab vedotin for use in relapsed Hodgkin lymphoma and systemic anaplastic large cell lymphoma. Nat Biotechnol 30:631-637
40. Francisco JA, Cerveny CG, Meyer DL et al (2003) cAC10-vcMMAE, an anti-CD30-monomethyl auristatin E conjugate with potent and selective antitumor activity. Blood 102:1458-1465
41. Younes A, Bartlett NL, Leonard JP et al (2010) Brentuximab vedotin (SGN-35) for relapsed CD30-positive lymphomas. N Engl J Med 363:1812-1821
42. Fanale MA, Forero-Torres A, Rosenblatt JD et al (2012) A phase I weekly dosing study of brentuximab vedotin in patients with relapsed/refractory CD30-positive hematologic malignancies. Clin Cancer Res J Am Assoc Cancer Res 18:248-255
43. Younes A, Gopal AK, Smith SE et al (2012) Results of a pivotal phase II study of brentuximab vedotin for patients with relapsed or refractory Hodgkin and other lymphoma. J Clin Oncol J Am Soc Clin Oncol 30:2183-2189
44. Minich SS (2012) Brentuximab vedotin: A new age in the treatment of Hodgkin lymphoma and anaplastic large cell lymphoma. Ann Pharmacother 46:377-383
45. Hynes NE, Stern DF (1994) The biology of erbB-2/neu/HER-2 and its role in cancer. Biochim Biophys Acta 1198:165-184
46. Dawood S, Broglio K, Buzdar AU et al (2010) Prognosis of women with metastatic breast cancer by HER2 status and trastuzumab treatment: An institutional-based review. J Clin Oncol J Am Soc Clin Oncol 28:92-98
47. Arteaga CL, Sliwkowski MX, Osborne CK et al (2012) Treatment of HER2-positive breast cancer: Current status and future perspectives. Nat Rev Clin Oncol 9:16-32
48. Tsang RY, Finn RS (2012) Beyond trastuzumab: Novel therapeutic strategies in HER2-positive metastatic breast cancer. Br J Cancer 106:6-13
49. Phillips GD, Li G, Dugger DL et al (2008) Targeting HER2-positive breast cancer with trastuzumab-DM1, an antibody-cytotoxic drug conjugate. Cancer Res 68:9280-9290
50. Junttila TT, Li G, Parsons K et al (2011) Trastuzumab-DM1 (T-DM1) retains all the mechanisms of action of trastuzumab and efficiently inhibits growth of lapatinib insensitive breast cancer. Breast Cancer Res Treat 128:347-356
51. Barok M, Tanner M, Koninki K et al (2011) Trastuzumab-DM1 causes tumour growth inhibition by mitotic catastrophe in trastuzumab-resistant breast cancer cells in vivo. Breast Cancer Res BCR 13:R46
52. Krop IE, Beeram M, Modi S et al (2010) 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 J Am Soc Clin Oncol 28:2698-2704
53. Beeram M, Krop IE, Burris HA et al (2012) A phase 1 study of weekly dosing of trastuzumab emtansine (T-DM1) in patients with advanced human epidermal growth factor 2-positive breast cancer. Cancer 118:5733-5740
54. Burris HA, Tibbitts J, Holden SN et al (2011) Trastuzumab emtansine (T-DM1): A novel agent for targeting HER2+ breast cancer. Clin Breast Cancer 11:275-282
55. Mathew J, Perez EA (2011) Trastuzumab emtansine in human epidermal growth factor receptor 2-positive breast cancer: A review. Curr Opin Oncol 23:594-600
56. Lorusso PM, Weiss D, Guardino E et al (2011) Trastuzumab emtansine: A unique antibody-drug conjugate in development for human epidermal growth factor receptor 2-positive cancer. Clin Cancer Res J Am Assoc Cancer Res 17:6437-6447
57. Burris HA, Rugo HS, Vukelja SJ et al (2011) Phase II study of the antibody drug conjugate trastuzumab-DM1 for the treatment of human epidermal growth factor receptor 2 (HER2)-positive breast cancer after prior HER2-directed therapy. J Clin Oncol J Am Soc Clin Oncol 29:398-405
58. Krop IE, Lorusso P, Miller KD et al (2012) A phase II study of trastuzumab emtansine in patients with human epidermal growth factor receptor 2-positive metastatic breast cancer who were previously treated with trastuzumab, lapatinib, an anthracycline, a taxane, and capecitabine. J Clin Oncol J Am Soc Clin Oncol 30:3234-3241
59. Girish S, Gupta M, Wang B et al (2012) Clinical pharmacology of trastuzumab emtansine (T-DM1): An antibody-drug conjugate in development for the treatment of HER2-positive cancer. Cancer Chemother Pharmacol 69:1229-1240
60. Gupta M, Lorusso PM, Wang B et al (2012) Clinical implications of pathophysiological and demographic covariates on the population pharmacokinetics of trastuzumab emtansine, a HER2-targeted antibody-drug conjugate, in patients with HER2-positive metastatic breast cancer. J Clin Pharmacol 52:691-703
61. Perez E, Dirix L, Kocsis J et al (2010) Efficacy and safety of trastuzumab-DM1 versus trastuzumab plus docetaxel in HER2-positive metastatic breast cancer patients with no prior chemotherapy for metastatic disease: Preliminary results of a randomized, multicenter, open-label phase 2 study (TDM4450g). Ann Oncol 21(Suppl 8):viii2, Abstract LBA3
62. Hurvitz S, Dirix L, Kocsis J et al (2011) Trastuzumab emtansine (T-DM1) vs trastuzumab plus docetaxel (H + T) in previouslyuntreated HER2-positive metastatic breast cancer (MBC): Primary results of a randomized, multicenter, open-label phase II study (TDM4450g/B021976). Eur J Cancer 47:ECCO-ESMO, Abstract 5001
63. Verma S, Miles D, Gianni L et al (2012) Trastuzumab emtansine for HER2-positive advanced breast cancer. N Engl J Med 367:1783-1791
64. Tedder TF, Poe JC, Haas KM (2005) CD22: A multifunctional receptor that regulates B lymphocyte survival and signal transduction. Adv Immunol 88:1-50
65. Shan D, Press OW (1995) Constitutive endocytosis and degradation of CD22 by human B cells. J Immunol 154:4466-4475
66. Wong BY, Dang NH (2010) Inotuzumab ozogamicin as novel therapy in lymphomas. Expert Opin Biol Ther 10:1251-1258
67. Thomas X (2012) Inotuzumab ozogamicin in the treatment of B-cell acute lymphoblastic leukemia. Expert Opin Investig Drugs 21:871-878
68. DiJoseph JF, Goad ME, Dougher MM et al (2004) Potent and specific antitumor efficacy of CMC-544, a CD22-targeted immunoconjugate of calicheamicin, against systemically disseminated B-cell lymphoma. Clin Cancer Res J Am Assoc Cancer Res 10:8620-8629
69. Advani A, Coiffier B, Czuczman MS et al (2010) Safety, pharmacokinetics, and preliminary clinical activity of inotuzumab ozogamicin, a novel immunoconjugate for the treatment of B-cell non-Hodgkin and other lymphoma: Results of a phase I study. J Clin Oncol J Am Soc Clin Oncol 28:2085-2093
70. Ogura M, Tobinai K, Hatake K et al (2010) Phase I study of inotuzumab ozogamicin (CMC-544) in Japanese patients with follicular lymphoma pretreated with rituximabbased therapy. Cancer Sci 101:1840-1845
71. DiJoseph JF, Dougher MM, Kalyandrug LB et al (2006) Antitumor efficacy 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 J Am Assoc Cancer Res 12:242-249
72. Dang N, Smith M, Offner F et al (2009) Anti-CD22 immunoconjugate inotuzumab ozogamicin (CMC-544) + rituximab: Clinical activity including survival in patients with recurrent/refractory follicular or "aggressive" lymphoma. Blood 114, Abstract 584
73. Fayad L, Patel H, Verhoef G et al (2008) Safety and clinical activity of the anti-CD22 immunoconjugate inotuzumab ozogamicin (CMC-544) in combination with rituximab in follicular lymphoma or diffuse large B-cell lymphoma: Preliminary report of a phase 1/2 study. Blood 112, Abstract 266
74. Verhoef G, Dang N, Smith M et al (2010) Anti-CD22 immunoconjugate inotuzumab ozogamicin (CMC-544) + rituximab: Clinical activity in patients with relapsed/refractory follicular or aggressive lymphomas. Haematologica 95, Abstract 0573
75. Jabbour E, O'Brien S, Thomas DA, Ravandi F et al (2011) Inotuzumab ozogamicin (IO; CMC544), a CD22 monoclonal antibody attached to calicheamycin, produces complete response (CR) plus complete marrow response (mCR) of greater than 50% in refractory relapse (R-R) acute lymphocytic leukemia (ALL). J Clin Oncol 29, Abstract 6507
76. Kantarjian H, Thomas D, Jorgensen J et al (2012) Inotuzumab ozogamicin, an anti-CD22-calecheamicin conjugate, for refractory and relapsed acute lymphocytic leukaemia: A phase 2 study. Lancet Oncol 13:403-411
77. Blanc V, Bousseau A, Caron A et al (2011) SAR3419: An anti-CD19-maytansinoid immunoconjugate for the treatment of B-cell malignancies. Clin Cancer Res J Am Assoc Cancer Res 17:6448-6458
78. Younes A, Kim S, Romaguera J et al (2012) Phase I multidose-escalation study of the anti-CD19 maytansinoid immunoconjugate SAR3419 administered by intravenous infusion every 3 weeks to patients with relapsed/ refractory B-cell lymphoma. J Clin Oncol J Am Soc Clin Oncol 30:2776-2782
79. Coiffier B, Morschhauser F, Dupuis J et al (2012) Phase I study cohort evaluating an optimized administration schedule of SAR3419, an anti-CD19 DM4-loaded antibody drug conjugate (ADC), in patients (pts) with CD19 positive relapsed/refractory b-cell non-Hodgkin's lymphoma (NCT00796731). J Clin Oncol 30, Abstract 8057
80. Hammer O (2012) CD19 as an attractive target for antibody-based therapy. MAbs 4:571-577
81. Keir CH, Vahdat LT (2012) The use of an antibody drug conjugate, glembatumumab vedotin (CDX-011), for the treatment of breast cancer. Expert Opin Biol Ther 12:259-263
82. Tse KF, Jeffers M, Pollack VA et al (2006) CR011, a fully human monoclonal antibody-Auristatin E conjugate, for the treatment of melanoma. Clin Cancer Res J Am Assoc Cancer Res 12:1373-1382
83. Naumovski L, Junutula JR (2010) Glembatumumab vedotin, a conjugate of an antiglycoprotein non-metastatic melanoma protein B mAb and monomethyl auristatin E for the treatment of melanoma and breast cancer. Curr Opin Mol Ther 12:248-257
84. Hamid O, Sznol M, Pavlick A et al (2010) Frequent dosing and GPNMB expression with CDX-011 (CR011-vcMMAE), an antibody-drug conjugate (ADC), in patients with advanced melanoma. J Clin Oncol 28, Abstract 8525
85. Szol M, Hamid O, Hwu P et al (2009) Pharmacokinetics of CR011-vcMMAE, an antibody-drug conjugate, in a phase I study of patients with advanced melanoma. J Clin Oncol 27, Abstract 9063
86. Saleh M, Bendell J, Rose et al (2010) Correlation of GPNMB expression with outcome in breast cancer (BC) patients treated with the antibody-drug conjugate (ADC), CDX-011 (CR011-vcMMAE). J Clin Oncol 28, Abstract 1095
87. Hoashi T, Sato S, Yamaguchi Y et al (2010) Glycoprotein nonmetastatic melanoma protein b, a melanocytic cell marker, is a melanosome-specific and proteolytically released protein. FASEB J 24:1616-1629
88. Akhtar NH, Pail O, Saran A et al (2012) Prostate-specific membrane antigen-based therapeutics. Adv Urol 2012:973820
89. Ghosh A, Heston WD (2004) Tumor target prostate specific membrane antigen (PSMA) and its regulation in prostate cancer. J Cell Biochem 91:528-539
90. Chang SS, Reuter VE, Heston WD et al (1999) Five different anti-prostate-specific membrane antigen (PSMA) antibodies confirm PSMA expression in tumor-Associated neovasculature. Cancer Res 59:3192-3198
91. Minner S, Wittmer C, Graefen M et al (2011) High level PSMA expression is associated with early PSA recurrence in surgically treated prostate cancer. Prostate 71:281-288
92. Silver DA, Pellicer I, Fair WR et al (1997) Prostate-specific membrane antigen expression in normal and malignant human tissues. Clin Cancer Res J Am Assoc Cancer Res 3:81-85
93. Wang X, Ma D, Olson WC et al (2011) In vitro and in vivo responses of advanced prostate tumors to PSMA ADC, an auristatinconjugated antibody to prostate-specific membrane antigen. Mol Cancer Ther 10:1728-1739
94. Galsky MD, Eisenberger M, Moore-Cooper S et al (2008) Phase I trial of the prostatespecific membrane antigen-directed immunoconjugate MLN2704 in patients with progressive metastatic castration-resistant prostate cancer. J Clin Oncol J Am Soc Clin Oncol 26:2147-2154
95. Petrylak D, Kantoff P, Mega-A et al (2012) Prostate-specific membrane antigen antibody drug conjugate (PSMA ADC): A phase I trial in men with prostate cancer previously treated with taxane. J Clin Oncol 30, Abstract 107
96. Petrylak D, Kantoff P, Frank R et al (2011) Prostate-specific membrane antigen antibody-drug conjugate (PSMA ADC): A phase I trial in taxane-refractory prostate cancer. J Clin Oncol 29, Abstract 4550
97. Petrylak D, Kantoff P, Mega-A et al (2012) Prostate specific membrane antigen antibody drug conjugate (PSMA ADC): A phase 1 trial in castration-resistant metastatic prostate cancer (mCRPC). EORTC-NCI-AACR 47
98. Wijdenes J, Vooijs WC, Clément C et al (1996) A plasmocyte selective monoclonal antibody (B-B4) recognizes syndecan-1. Br J Haematol 94:318-323
99. Tassone P, Goldmacher VS, Neri P et al (2004) Cytotoxic activity of the maytansinoid immunoconjugate B-B4-DM1 against CD138+ multiple myeloma cells. Blood 104:3688-3696
100. Jagannath S, Chanan-Khan A, Heffner L et al (2011) BT062, an antibody-drug conjugate directed against CD138, shows clinical activity in a phase I study in patients with relapsed or relapsed/refractory multiple myeloma. ASH Annual Meeting, Abstract 305
101. Lutz RJ, Whiteman KR (2009) Antibody-maytansinoid conjugates for the treatment of myeloma. MAbs 1:548-551
102. Chanan-Khan A, Wolf J, Gharibo M. et al (2009) Phase I study of IMGN901, used as monotherapy, in patients with heavily pretreated CD56-positive multiple myeloma -A preliminary safety and efficacy analysis. ASH Annual Meeting, Abstract 2883
103. Woll P, Laurigan P, O'Brien M et al (2009) Clinical experience of IMGN901 (BB-10901, huN901-DM1) in patients with Merkel cell carcinoma (MCC). Mol Cancer Ther 8, Abstract B237
104. Woll PJ, O'Brien M, Fossella F et al (2010) Phase I study of lorvotuzumab mertansine (IMGN901) in patients with CD56-positive solid tumors. Ann Oncol J Eur Soc Med Oncol ESMO, Abstract 536
105. Berdeja J, Ailawadhi S, Niesvizky R et al (2010) Phase I study of lorvotuzumab mertansine (IMGN901) used in combination with lenalidomide and dexamethasone in patients with CD56-positive multiple myeloma, a preliminary safety and efficacy analysis of the combination. ASHAnnual Meeting, Abstract 1934
106. Berdeja J, Mace J, Lamar R et al (2012) A single-Arm, open-label, multicenter phase I/ II study of the combination of panobinostat (pan) and carfilzomib (cfz) in patients (pts) with relapsed/refractory multiple myeloma (RR MM). J Clin Oncol 30, Abstract TPS8115
107. Mao W, Tien J, Goldenberg D et al (2010) Early study on LGR5/GPR49 molecule as a potential colon cancer stem cell target for the antibody conjugated drug treatment. Annual Meeting of the AACR, Abstract 4289
108. Schliemann C, Neri D (2010) Antibodybased vascular tumor targeting. Recent Results Cancer Res 180:201-216
109. Terrett J, Devasthali V, Pan C et al (2008) Ptk7 as a direct and tumor stroma target in multiple solid malignancies. Annual Meeting of the AACR, Abstract 1526
110. Vater C, Manning C, Millar H et al (2008) Anti-tumor efficacy of the integrin-targeted immunoconjugate IMGN388 in preclinical models. EORTC-NCI-AACR, Abstract ENA-0399
111. Thon JN, Devine MT, Begonja AJ et al (2012) High-content live-cell imaging assay used to establish mechanism of trastuzumab emtansine (T-DM1)-mediated inhibition of platelet production. Blood 120:1975-1984
112. Kovtun YV, Audette CA, Mayo MF et al (2010) Antibody-maytansinoid conjugates designed to bypass multidrug resistance. Cancer Res 70:2528-2537
113. Erickson HK, Lambert JM (2012) ADME of antibody-maytansinoid conjugates. AAPS J 14:799-805
114. Erickson HK, Phillips GD, Leipold DD et al (2012) The effect of different linkers on target cell catabolism and pharmacokinetics/pharmacodynamics of trastuzumab maytansinoid conjugates. Mol Cancer Ther 11:1133-1142
115. Lin K, Tibbitts J (2012) Pharmacokinetic considerations for antibody drug conjugates. Pharm Res 29:2354-2366
116. Junutula JR, Raab H, Clark S et al (2008) Site-specific conjugation of a cytotoxic drug to an antibody improves the therapeutic index. Nat Biotechnol 26:925-932
117. McDonagh CF, Turcott E,Westendorf L et al (2006) Engineered antibody-drug conjugates with defined sites and stoichiometries of drug attachment. Protein Eng Design Select PEDS 19:299-307
118. Zhao RY, Wilhelm SD, Audette C et al (2011) Synthesis and evaluation of hydrophilic linkers for antibody-maytansinoid conjugates. J Med Chem 54:3606-3623
119. Moldenhauer G, Salnikov AV, Luttgau AV et al (2012) Therapeutic potential of amanitin-conjugated anti-epithelial cell adhesion molecule monoclonal antibody against pancreatic carcinoma. J Natl Cancer Inst 104:622-634
120. Kim KM, McDonagh CF, Westendorf L et al (2008) Anti-CD30 diabody-drug conjugates with potent antitumor activity. Mol Cancer Ther 7:2486-2497
121. Wittrup KD, Thurber GM, SchmidtMMet al (2012) Practical theoretic guidance for the design of tumor-targeting agents. Methods Enzymol 503:255-268
122. Annunziata CM, Kohn EC, Lorusso P et al (2012) Phase 1, open-label study of MEDI-547 in patients with relapsed or refractory solid tumors. Invest New Drugs 31:77-84
123. Milowsky M, Galsky M, George M et al (2006) Phase I/II trial of the prostate-specific membrane antigen (PSMA)-targeted immunoconjugate MLN2704 in patients (pts) with progressive metastatic castration resistant prostate cancer (CRPC). J Clin Oncol 24, Abstract 4500
124. Chan SY, Gordon AN, Coleman RE et al (2003) A phase 2 study of the cytotoxic immunoconjugate CMB-401 (hCTM01-calicheamicin) in patients with platinumsensitive recurrent epithelial ovarian carcinoma. Cancer Immunol Immunother CII 52:243-248
125. Gillespie AM, Broadhead TJ, Chan SY et al (2000) Phase I open study of the effects of ascending doses of the cytotoxic immunoconjugate CMB-401 (hCTMO1-calicheamicin) in patients with epithelial ovarian cancer. Ann Oncol J Eur Soc Med Oncol ESMO 11:735-741