Drug conjugates such as antibody drug conjugates (ADCs), immunotoxins and immunoliposomes challenge daily clinical practice

International Journal of Molecular Sciences

Volumn 13, Issue 12, 2012, Pages 16785-16795

  Janthur, Wolf Dieter ^a   Cantoni, Nathan ^a   Mamot, Christoph ^a  

^a CANTONAL HOSPITAL AARAU   (Switzerland)

Author keywords

Antibody drug conjugates; Drug conjugates; Immunoliposomes; Immunotoxins; Targeted therapy

Indexed keywords

AMATUXIMAB; ANTHRACYCLINE DERIVATIVE; ANTIBODY CONJUGATE; ANTIGEN; ANTINEOPLASTIC AGENT; AURISTATINE; BRENTUXIMAB VEDOTIN; CALICHEAMICIN; CYTOTOXIC AGENT; DENILEUKIN DIFTITOX; DOXORUBICIN; FIRTECAN; GEMTUZUMAB OZOGAMICIN; IMMUNOLIPOSOME; IMMUNOTOXIN; INOTUZUMAB OZOGAMICIN; IRINOTECAN; LIPOSOME; LORVOTUZUMAB MERTANSINE; MACROGOL; MAYTASINE; MILATUZUMAB; MOXETUMOMAB PASUDOTOX; OPORTUZUMAB MONATOX; RFB4 PE38; RICIN; TAXANE DERIVATIVE; TRASTUZUMAB EMTANSINE; UNCLASSIFIED DRUG; UNINDEXED DRUG; VORSETUZUMAB MAFODOTIN; CAC10-VCMMAE; MAYTANSINE; MONOCLONAL ANTIBODY;

ACUTE GRANULOCYTIC LEUKEMIA; ACUTE LYMPHOBLASTIC LEUKEMIA; ANGIOIMMUNOBLASTIC T CELL LYMPHOMA; BLADDER CANCER; BLOOD TOXICITY; BREAST CANCER; CANCER IMMUNOTHERAPY; CHRONIC LYMPHATIC LEUKEMIA; CLINICAL PRACTICE; CUTANEOUS T CELL LYMPHOMA; DIARRHEA; DRUG CONJUGATION; DRUG DELIVERY SYSTEM; DRUG MECHANISM; DRUG TARGETING; FATIGUE; HAIRY CELL LEUKEMIA; HEMATOLOGIC MALIGNANCY; HEMOLYTIC UREMIC SYNDROME; HODGKIN DISEASE; HUMAN; KAPOSI SARCOMA; KIDNEY CARCINOMA; LARGE CELL LYMPHOMA; LUNG NON SMALL CELL CANCER; LYMPHOMA; MELANOMA; MESOTHELIOMA; MULTIPLE CYCLE TREATMENT; MULTIPLE MYELOMA; NAUSEA; NEUTROPENIA; NONHODGKIN LYMPHOMA; OVARY CANCER; PANCREAS CANCER; PHASE 1 CLINICAL TRIAL (TOPIC); PHASE 2 CLINICAL TRIAL (TOPIC); PHASE 3 CLINICAL TRIAL (TOPIC); REVIEW; SENSORY NEUROPATHY; SOLID TUMOR; THROMBOCYTOPENIA; TUMOR CELL; VOMITING; ANALOGS AND DERIVATIVES; ANIMAL; IMMUNOLOGY; NEOPLASMS;

ANIMALS; ANTIBODIES, MONOCLONAL, HUMANIZED; ANTINEOPLASTIC AGENTS; HUMANS; IMMUNOCONJUGATES; IMMUNOTOXINS; LIPOSOMES; MAYTANSINE; NEOPLASMS;

EID: 84871698293     PISSN: 16616596     EISSN: 14220067     Source Type: Journal    
DOI: 10.3390/ijms131216020     Document Type: Review

References (155)

1. NCT00085709: S0106 cytarabine and daunorubicin with or without gemtuzumab ozogamicin followed by high-dose cytarabine followed by either gemtuzumab ozogamicin or no additional therapy in treating patients with previously untreated de novo acute Myeloid Leukemia. Southwest Oncology Group, Ann Arbor, MI, USA, Unpublished work, 2010.
2. Brentuximab vedotin. Drugs R. D. 2011, 11, 85-95.
3. Mathew, J.; Perez, E.A. Trastuzumab emtansine in human epidermal growth factor receptor 2-positive breast cancer: a review. Curr. Opin. Oncol. 2011, 23, 594-600.
4. Choudhary, S.; Mathew, M.; Verma, R.S. Therapeutic potential of anticancer immunotoxins. Drug Discov. Today 2011, 16, 495-503.
5. Kreitman, R.J.; Wilson, W.H., Bergeron, K.; Raggio, M.; Stetler-Stevenson, M.; FitzGerlad, D.J.; Pastan, I. Efficacy of the anti-CD22 recombinant immunotoxin BL22 in chemotherapy-resistant hairy-cell leukemia. N. Engl. J. Med. 2001, 345, 241-247.
6. Matsumura, Y.; Maeda, H. A new concept for macromolecular therapeutics in cancer chemotherapy: Mechanism of tumoritropic accumulation of proteins and the antitumor agent smancs. Cancer Res. 1986, 46, 6387-6392.
7. Jain, R.K. Transport of molecules across tumor vasculature. Cancer Metastasis Rev. 1987, 6, 559-593.
8. Jain, R.K. Transport of molecules, particles, and cells in solid tumors. Annu. Rev. Biomed. Eng. 1999, 1, 241-263.
9. Gerber, H.P.; Senter, P.D.; Senter, P.D.; Grewal, I.S. Antibody drug-conjugates targeting the tumor vasculature: Current and future developments. mAbs 2009, 1, 247-253.
10. Mukherjee, S.; Ghosh, R.N.; Maxfield, F.R. Endocytosis. Physiol. Rev. 1997, 77, 759-803.
11. Scott, A.M.; Wolchok, J.D.; Old, L.J. Antibody therapy of cancer. Nat. Rev. Cancer 2012, 12, 278-287.
12. Curiel, T.J. Immunotherapy: A useful strategy to help combat multidrug resistance. Drug Resist. Updat. 2012, 15, 106-113.
13. Arnon, R. Site-directed tumor chemotherapy. Compr. Ther. 1978, 4, 68-73.
14. Mamot, C.; Drummond, D.C.; Hong, K.; Kirpotin, D.B.; Park, J.W. Liposome-based approaches to overcome anticancer drug resistance. Drug Resist. Updat. 2003, 6, 271-279.
15. Maruyama, K. PEG-liposome in DDS and clinical studies. Nihon Rinsho 1998, 56, 632-637.
16. Huwyler, J.; Cerletti, A.; Fricker, G.; Eberle, A.N.; Drewe, J. By-passing of P-glycoprotein using immunoliposomes. J. Drug Target. 2002, 10, 73-79.
17. Berezov, T.T.; Iaglova, N.V.; Dmitrieva, T.B.; Zhirkov Lu, A.; Chekhonin, V.P. Liposome-oriented transport of therapeutic drugs. Vestn. Ross. Akad. Med. Nauk. 2004, 42-47.
18. Maclean, A.; Symonds, G.; Ward, A. Immunoliposomes as targeted delivery vehicles for cancer therapeutics (Review). Int. J. Oncol. 1997, 11, 325-332.
19. Golay, J.; Introna, M. Mechanism of action of therapeutic monoclonal antibodies: Promises and pitfalls of in vitro and in vivo assays. Arch. Biochem. Biophys. 2012, 526, 146-153.
20. Alley, S.C.; Okeley, N.M.; Senter, P.D. Antibody-drug conjugates: Targeted drug delivery for cancer. Curr. Opin. Chem. Biol. 2010, 14, 529-537.
21. Chari, R.V.; Jackel, K.A.; Bourret, L.A.; Derr, S.M.; Tadayoni, B.M.; Mattocks, K.M.; Shah, S.A.; Liu, C.; Blattler, W.A.; Goldmacher, V.S. Enhancement of the selectivity and antitumor efficacy of a CC-1065 analogue through immunoconjugate formation. Cancer Res. 1995, 55, 4079-4084.
22. Schmidt, M.M.; Wittrup, K.D. A modeling analysis of the effects of molecular size and binding affinity on tumor targeting. Mol. Cancer Ther. 2009, 8, 2861-2871.
23. Attarwala, H. Role of antibodies in cancer targeting. J. Nat. Sci. Biol. Med. 2010, 1, 53-56.
24. Hamblett, K.J.; Senter, P.D.; Chace, D.F.; Sun, M.M.; Lenox, J.; Cerveny, C.G.; Kissler, K.M.; Bernhardt, S.X.; Kopcha, A.K.; Zabinski, R.F.; et al. Effects of drug loading on the antitumor activity of a monoclonal antibody drug conjugate. Clin. Cancer Res. 2004, 10, 7063-7070.
25. Shen, B.Q.; Xu, K.; Liu, L.; Raab, H.; Bhakta, S.; Kenrick, M.; Parsons-Reponte, K. L; Tien, J.; Yu, S.F.; Mai, E.; et al. Conjugation site modulates the in vivo stability and therapeutic activity of antibody-drug conjugates. Nat. Biotechnol. 2012, 30, 184-189.
26. Junutula, J.R.; Raab, H.; Clark, S.; Bhakta, S.; Leipold, D.D.; Weir, S.; Chen, Y.; Simpson, M.; Tsai, S.P.; Dennis, M.S.; et al. Site-specific conjugation of a cytotoxic drug to an antibody improves the therapeutic index. Nat. Biotechnol. 2008, 26, 925-932.
27. Axup, J.Y.; Bajjuri, K.M.; Ritland, M.; Hutchins, B.M.; Kim.C.H.; Kazane, S.A.; Halder, R.; Forstyth, J.S.; Santidrian, A.F.; Stafin, K.; et al. Synthesis of site-specific antibody-drug conjugates using unnatural amino acids. Proc. Natl. Acad. Sci. USA 2012, 109, 16101-16106.
28. Jeffrey, S.C.; Torgov, M.Y.; Andreyka, J.B.; Boddington, L.; Cerveny, C.G.; Denny, W.A.; Gordon, K.A.; Gustin, G.; Haugen, J.; Kline, T.; et al. Design, synthesis, and in vitro evaluation of dipeptide-based antibody minor groove binder conjugates. J. Med. Chem. 2005, 48, 1344-1358.
29. Miller, M.L.; Roller, E.E.; Wu, X.; Leece, B.A.; Goldmacher, V.S.; Chari, R.V.; Ojima, I.; Synthesis of potent taxoids for tumor-specific delivery using monoclonal antibodies. Bioorg. Med. Chem. Lett. 2004, 14, 4079-4082.
30. Senter, P.D. Activation of prodrugs by antibody-enzyme conjugates: A new approach to cancer therapy. FASEB J. 1990, 4, 188-193.
31. Alley, S.C.; Benjamin, D.R.; Jeffrey, S.C.; Okeley, N.M.; Meyer, D.L.; Sanderson, R.J.; Senter, P.D. Contribution of linker stability to the activities of anticancer immunoconjugates. Bioconjug. Chem. 2008, 19, 759-765.
32. Ducry, L.; Stump, B. Antibody-drug conjugates: Linking cytotoxic payloads to monoclonal antibodies. Bioconjug. Chem. 2010, 21, 5-13.
33. Doronina, S.O.; Mendelsohn, B.A.; Bovee, T.D.; Cerveny, C.G.; Alley, S.C.; Meyer, D.L.; Oflazoglu, E.; Toki, B.E.; Sanderson, R.J.; Zabinsky, R.F.; et al. Enhanced activity of monomethylauristatin F through monoclonal antibody delivery: Effects of linker technology on efficacy and toxicity. Bioconjug. Chem. 2006, 17, 114-124.
34. Chari, R.V. Targeted cancer therapy: Conferring specificity to cytotoxic drugs. Acc. Chem. Res. 2008, 41, 98-107.
35. Chari, R.V.; Martell, B.A.; Gross, J.L.; Cook, S.B.; Shah, S.A.; Blattler, W.A.; McKenzie, S.J.; Goldmacher, V.S. Immunoconjugates containing novel maytansinoids: Promising anticancer drugs. Cancer Res. 1992, 52, 127-131.
36. Simmons, T.L.; Andrianasolo, E.; McPhail, K.; Flatt, P.; Gerwick, W.H. Marine natural products as anticancer drugs. Mol. Cancer Ther. 2005, 4, 333-342.
37. Widdison, W.C.; Wilhelm, S.D.; Cavanagh, E.E.; Whiteman, K.R.; Leece, B.A.; Kovtun, Y.; Goldmacher, V.S.; Xie, H.; Steeves, R.M.; Lutz, R.J.; et al. Semisynthetic maytansine analogues for the targeted treatment of cancer. J. Med. Chem. 2006, 49, 4392-4408.
38. Thorson, J.S.; Sievers, E.L.; Ahlert, J.; Shepard, E.; Whitwam, R.E.; Onwueme, K.C.; Ruppen, M. Understanding and exploiting nature's chemical arsenal: The past, present and future of calicheamicin research. Curr. Pharm. Des. 2000, 6, 1841-1879.
39. Hamann, P.R.; Hinman, L.M.; Hollander, I.; Beyer, C.F.; Lindh, D.; Holcomb, R.; Hallett, W.; Tsou, H.R.; Upeslacis, J.; Shochat, D.; et al. Gemtuzumab ozogamicin, a potent and selective anti-CD33 antibody-calicheamicin conjugate for treatment of acute myeloid leukemia. Bioconjug. Chem. 2002, 13, 47-58.
40. Ricart, A.D. Antibody-drug conjugates of calicheamicin derivative: Gemtuzumab ozogamicin and inotuzumab ozogamicin. Clin. Cancer Res. 2011, 17, 6417-6427.
41. Govindan, S.V.; Goldenberg, D.M. New antibody conjugates in cancer therapy. ScientificWorldJournal 2010, 10, 2070-2089.
42. Mathijssen, R.H.; van Alphen, R.J.; Verweij, J.; Loos, W.J.; Nooter, K.; Stoter, G.; Sparreboom, A. Clinical pharmacokinetics and metabolism of irinotecan (CPT-11). Clin. Cancer Res. 2001, 7, 2182-2194.
43. Rivory, L.P. Metabolism of CPT-11. Impact on activity. Ann. N. Y. Acad. Sci. 2000, 922, 205-215.
44. Kreitman, R.J. Immunotoxins for targeted cancer therapy. AAPS J. 2006, 8, E532-E551.
45. Pastan, I.; Hassan, R.; Fitzgerald, D.J.; Kreitman, R.J. Immunotoxin therapy of cancer. Nat. Rev. Cancer 2006, 6, 559-565.
46. Tsukazaki, K.; Hayman, E.G.; Ruoslahti, E. Effects of ricin A chain conjugates of monoclonal antibodies to human alpha-fetoprotein and placental alkaline phosphatase on antigen-producing tumor cells in culture. Cancer Res. 1985, 45, 1834-1838.
47. Smallshaw, J.E.; Ghetie, V.; Rizo, J.; Fulmer, J.R.; Trahan, L.L.; Ghetie, M.A.; Vitetta, M.S. Genetic engineering of an immunotoxin to eliminate pulmonary vascular leak in mice. Nat. Biotechnol. 2003, 21, 387-391.
48. FitzGerald, D.J.; Kreitman, R.; Wilson, W.; Squires, D.; Pastan, I. Recombinant immunotoxins for treating cancer. Int. J. Med. Microbiol. 2004, 293, 577-582.
49. Mathew, M.; Verma, R.S. Humanized immunotoxins: A new generation of immunotoxins for targeted cancer therapy. Cancer Sci. 2009, 100, 1359-1365.
50. Park, J.W.; Hong, K.; Kirpotin, D.B.; Papahadjopoulos, D.; Benz, C.C. Immunoliposomes for cancer treatment. Adv. Pharmacol. 1997, 40, 399-435.
51. Torchilin, V.P. Recent approaches to intracellular delivery of drugs and DNA and organelle targeting. Annu. Rev. Biomed. Eng. 2006, 8, 343-375.
52. Sofou, S.; Sgouros, G. Antibody-targeted liposomes in cancer therapy and imaging. Expert. Opin. Drug Deliv. 2008, 5, 189-204.
53. Cheng, W.W.; Allen, T.M. The use of single chain Fv as targeting agents for immunoliposomes: An update on immunoliposomal drugs for cancer treatment. Expert Opin. Drug Deliv. 2010, 7, 461-478.
54. Milla, P.; Dosio, F.; Cattel, L. PEGylation of proteins and liposomes: A powerful and flexible strategy to improve the drug delivery. Curr. Drug Metab. 2012, 13, 105-119.
55. Ng, K.; Zhao, L.; Liu, Y.; Mahapatro, M. The effects of polyethyleneglycol (PEG)-derived lipid on the activity of target-sensitive immunoliposome. Int. J. Pharm. 2000, 193, 157-166.
56. Huang, S.K.; Lee, K.D.; Hong, K.; Friend, D.S.; Papahadjopoulos, D. Microscopic localization of sterically stabilized liposomes in colon carcinoma-bearing mice. Cancer Res. 1992, 52, 5135-5143.
57. Working, P.K.; Dayan, A.D. Pharmacological-toxicological expert report. CAELYX. (Stealth liposomal doxorubicin HCl). Hum. Exp. Toxicol. 1996, 15, 751-785.
58. Siegal, T.; Horowitz, A.; Gabizon, A. Doxorubicin encapsulated in sterically stabilized liposomes for the treatment of a brain tumor model: biodistribution and therapeutic efficacy. J. Neurosurg. 1995, 83, 1029-1037.
59. Mamot, C.; Drummond, D.C.; Greiser, U.; Hong, K.; Kirpotin, D.B.; Marks, J.D.; Park, J.W.; Epidermal growth factor receptor (EGFR)-targeted immunoliposomes mediate specific and efficient drug delivery to EGFR-and EGFRvIII-overexpressing tumor cells. Cancer Res. 2003, 63, 3154-3161.
60. Northfelt, D.W.; Dezube, B.J.; Thommes, J.R.; Levine, R.; von Roenn, J.H.; Dosik, G.M.; Rios, A.; Krown, S.E.; DuMond, C.; Mamelok, R.D. Efficacy of pegylated-liposomal doxorubicin in the treatment of AIDS-related Kaposi's sarcoma after failure of standard chemotherapy. J. Clin. Oncol. 1997, 15, 653-659.
61. Park, J.W. Liposome-based drug delivery in breast cancer treatment. Breast Cancer Res. 2002, 4, 95-99.
62. Mohrbacher, A.F.; Gregory, S.A.; Gabriel, D.A.; Rusk, J.M.; Giles, F.J. Liposomal daunorubicin (DaunoXome) plus dexamethasone for patients with multiple myeloma. A phase II International Oncology Study Group study. Cancer 2002, 94, 2645-2652.
63. Aviles, A.; Neri, N.; Castaneda, C.; Talavera, A.; Huerta-Guzman, J.; Gonzalez, M. Pegylated liposomal doxorubicin in combination chemotherapy in the treatment of previously untreated aggressive diffuse large-B-cell lymphoma. Med. Oncol. 2002, 19, 55-58.
64. Sarris, A.H.; Hagemeister, F.; Romaguera, J.; Rodriguez, M.A.; McLaughlin, P.; Tsimberidou, A.M.; Medeiros, L.J.; Samuels, B.; Pate, O.; Oholendt, M.; et al. Liposomal vincristine in relapsed non-Hodgkin's lymphomas: Early results of an ongoing phase II trial. Ann. Oncol. 2000, 11, 69-72.
65. Yang, T.; Cui, F.D.; Choi, M.K.; Choi, J.W.; Chung, S.J.; Shim, C.K.; Kim, D.D. Enhanced solubility and stability of PEGylated liposomal paclitaxel: In vitro and in vivo evaluation. Int. J. Pharm. 2007, 338, 317-326.
66. Kullberg, M.; Mann, K.; Anchordoquy, T.J. Targeting Her-2+ breast cancer cells with bleomycin immunoliposomes linked to LLO. Mol. Pharm. 2012, doi:10.1021/mp300049n.
67. Emerson, D.L. Liposomal delivery of camptothecins. Pharm. Sci. Technol. Today 2000, 3, 205-209.
68. Shapira, J.; Budman, D.; Bradley, T.; Gralla, R. Evolving lipid-based delivery systems in the management of neoplastic disease. Oncol. Rev. 2009, 3, 113-124.
69. Adair, J.R.; Howard, P.W.; Hartley, J.A.; Williams, D.G.; Chester, K.A. Antibody-drug conjugates-a perfect synergy. Expert Opin. Biol. Ther. 2012.
70. Hosokawa, S.; Tagawa, T.; Niki, H.; Hirakawa, Y.; Nohga, K.; Nagaike, K. Efficacy of immunoliposomes on cancer models in a cell-surface-antigen-density-dependent manner. Br. J. Cancer 2003, 89, 1545-1551.
71. Barrajón-Catalán, E.; Menéndez-Gutiérrez, M.P.; Falcó, A.; Saceda, M.; Catania, A.; Micol, V. Immunoliposomes: A Multipurpose Strategy in Breast Cancer Targeted Therapy. In Breast Cancer-Current and Alternative Therapeutic Modalities; Gunduz, E., Gunduz, M., Eds.; InTech: Rijeka, Croatia, 2011.
72. Polson, A.G.; Calemine-Fenaux, J.; Chan, P.; Chang, W.; Christensen, E.; Clark, S.; de Sauvage, F.J.; Eaton, D.; Elkins, K.; Elliott, J.M.; et al. Antibody-drug conjugates for the treatment of non-Hodgkin's lymphoma: Target and linker-drug selection. Cancer Res. 2009, 69, 2358-2364.
73. Erickson, H.K.; Lewis Phillips, G.D.; Leipold, D.D.; Provenzano, C.A.; Mai, E.; Johnson, H.A.; Gunter, B.; Audette, C.A.; Gupta, M.; Pinkas, J.; et al. The effect of different linkers on target cell catabolism and pharmacokinetics/pharmacodynamics of trastuzumab maytansinoid conjugates. Mol. Cancer Ther. 2012, 11, 1133-1142.
74. Maruyama, K.; Kennel, S.J.; Huang, L. Lipid composition is important for highly efficient target binding and retention of immunoliposomes. Proc. Natl. Acad. Sci. USA 1990, 87, 5744-5748.
75. Legrand, O. An open label dose escalation study of AVE9633 administered as a single agent by intravenous (IV) infusion weekly for 2 weeks in 4-week cycle to patients with relapsed or refractory CD33-positive acute myeloid leukemia (AML). Blood 2007, 110, 1850.
76. Younes, A.; Kim, S.; Romaguera, J.; Copeland, A.; Farial, S.D.; Kwak, L.W.; Fayad, L.; Hagemeister, F.; Fanale, M.; Neelapu, S.; et al. 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. 2012, 30, 2776-2782.
77. Chen, Q.; Millar, H.J.; McCabe, F.L.; Manning, C.D.; Steeves, R.; Lai, K.; Kellogg, B.; Lutz, R.J.; Trikha, M.; Nakada, M.T.; et al. Alphav integrin-targeted immunoconjugates regress established human tumors in xenograft models. Clin. Cancer Res. 2007, 13, 3689-3695.
78. Gong, Y.P.; Yarrow, P.M.; Carmalt, H.L.; Kwun, S.Y.; Kennedy, C.W.; Lin, B.P.; Xing, P.X.; Gillett, D.J. Overexpression of Cripto and its prognostic significance in breast cancer: A study with long-term survival. Eur. J. Surg. Oncol. 2007, 33, 438-443.
79. Law, C.L.; Gordon, K.A.; Toki, B.E.; Yamane, A.K.; Hering, M.A.; Cerveny, C.G.; Petroziello, J.M.; Ryan, M.C.; Smith, L.; Simon, R.; et al. Lymphocyte activation antigen CD70 expressed by renal cell carcinoma is a potential therapeutic target for anti-CD70 antibody-drug conjugates. Cancer Res. 2006, 66, 2328-2337.
80. Annunziata, C.M.; Kohn, E.C.; Lorusso, P.; Houston, N.D.; Coleman, R.L.; Buzoianu, M.; Robbie, G.; Lechleider, R. Phase 1, open-label study of MEDI-547 in patients with relapsed or refractory solid tumors. Invest. New Drugs 2012, 30, 1-8.
81. Schnell, R.; Staak, O.; Borchmann, P.; Schartz, C.; Matthey, B.; Hansen, H.; Schindler, J.; Ghetie, V.; Vitetta, E.S.; Diehl, V.; et al. A Phase I study with an anti-CD30 ricin A-chain immunotoxin (Ki-4. dgA) in patients with refractory CD30+ Hodgkin's and non-Hodgkin's lymphoma. Clin. Cancer Res. 2002, 8, 1779-1786.
82. Raza, A.; Jurcic, J.G.; Roboz, G.J.; Maris, M.; Stephenson, J.J.; Wood, B.L.; Feldmann, E.J.; Galili, N.; Grove, L.E.; Drachmann, J.G.; et al. Complete remissions observed in acute myeloid leukemia following prolonged exposure to lintuzumab: A phase 1 trial. Leuk. Lymphoma 2009, 50, 1336-1344.
83. Younes, A.; Bartlett, N.L.; Leonard, J.P.; Kennedy, D.A.; Lynch, C.M.; Sievers, E.L.; Forero-Torres, A. Brentuximab vedotin (SGN-35) for relapsed CD30-positive lymphomas. N. Engl. J. Med. 2010, 363, 1812-1821.
84. Fanale, M.A.; Forero-Torres, A.; Rosenblatt, J.D.; Advani, R.H.; Franklin, A.R.; Kennedy, D.A.; Han, T.H.; Sievers, E.L.; Bartlett, N.L. A phase I weekly dosing study of brentuximab vedotin in patients with relapsed/refractory CD30-positive hematologic malignancies. Clin. Cancer Res. 2012, 18, 248-255.
85. Ma, D.; Hopf, C.E.; Malewicz, A.D.; Donovan, G.P.; Senter, P.D.; Goeckeler, W.F.; Maddon, P.J.; Olson, W.C. Potent antitumor activity of an auristatin-conjugated, fully human monoclonal antibody to prostate-specific membrane antigen. Clin. Cancer Res. 2006, 12, 2591-2596.
86. Al-Ahmadie, H.A.; Alden, D.; Qin, L.X.; Olgac, S.; Fine, S.W.; Gopalan, A.; Russo, P.; Motzer, R.J.; Reuter, V.E.; Tickoo, S.K. Carbonic anhydrase IX expression in clear cell renal cell carcinoma: An immunohistochemical study comparing 2 antibodies. Am. J. Surg. Pathol. 2008, 32, 377-382.
87. Chanan-Khan, A. Phase 1 Study of IMGN901, used as monotherapy, in patients with heavily pre-treated CD56-positive multiple myeloma. A preliminary safety and efficacy analysis. Blood 2009, ASH Annual Meeting Abstracts, Abstract: 2283.
88. Fossella, F. Investigation of IMGN901 in CD56+ 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, USA, 31 July-4 August 2009.
89. Chanan-Khan, A. Phase 1 Study of BT062 given as repeated single dose once every 3 weeks in patients with relapsed or relapsed/refractory multiple myeloma. Blood 2009, ASH Annual Meeting Abstracts, Abstract: 1862.
90. Ikeda, H.; Hideshima, T.; Fulciniti, M.; Lutz, R.J.; Yasui, H.; Okawa, Y.; Kiziltepe, T.; Vallet, S.; Pozzi, S.; Santo, L.; et al. The monoclonal antibody nBT062 conjugated to cytotoxic Maytansinoids has selective cytotoxicity against CD138-positive multiple myeloma cells in vitro and in vivo. Clin. Cancer Res. 2009, 15, 4028-4037.
91. Von Minckwitz, G.; Harder, S.; Hovelmann, S.; Jager, E.; Al-Batran, S.E.; Loibl, S.; Atmaca, A.; Cimpoiasu, C.; Neumann, A.; Abera, A.; et al. Phase I clinical study of the recombinant antibody toxin scFv(FRP5)-ETA specific for the ErbB2/HER2 receptor in patients with advanced solid malignomas. Breast Cancer Res. 2005, 7, R617-R626.
92. Petrul, H.M.; Schatz, C.A.; Kopitz, C.C.; Adnane, L.; McCabe, T.J.; Trail, P.; Ha, S.; Chang, Y.S.; Voznesensky, A.; Ranges, G.; et al. Therapeutic mechanism and efficacy of the antibody-drug conjugate BAY 79-4620 targeting human carbonic anhydrase 9. Mol. Cancer Ther. 2012, 11, 340-349.
93. Gudas, J.M. ASG-5ME: A novel antibody-drug conjugate (ADC) therapy for prostate, pancreatic, and gastric cancers. Presented at the ASCO 2010, Chicago, USA, 2010, Abstract No.: 230.
94. Gudas, J. Use of AGS-16M8F as a novel antibody drug conjugate (ADC) for treating renal cancers. J. Clin. Oncol. 2010, 28(suppl.), abstr e15014.
95. Ansell, S. Targeting CD70 in non-Hodgkin lymphoma and renal cell carcinoma: a phase 1 study of the antibody-drug conjugate SGN-75. Presented at the 35th ESMO Congress, Chicago, USA, 2010.
96. Advani, A.; Coiffier, B.; Czuczman, M.S.; Dreyling, M.; Foran, J.; Gine, E.; Gisselbrecht, C.; Ketterer, N.; Nasta, S.; Rohatiner, A.; et al. Safety, pharmacokinetics, and preliminary clinical activity of inotuzumab ozogamicin, a novel immunoconjugate for the treatment of B-cell non-Hodgkin's lymphoma: results of a phase I study. J. Clin. Oncol. 2010, 28, 2085-2093.
97. Rodon, J.; Garrison, M.; Hammond, L.E.; de Bono, J.; Smith, L:, Forero, L.; Hao, D.; Takimoto, C.; Lambert, J.M.; Pandite, L.; et al. Cantuzumab mertansine in a three-times a week schedule: A phase I and pharmacokinetic study. Cancer Chemother. Pharmacol. 2008, 62, 911-919.
98. Frolich, D.; Blabetafeld, D.; Reiter, K.; Giesecke, C.; Daridon, C.; Mei, H.E.; Burmester, G.R.; Goldenberg, D.M.; Salama, A.; Dorner, T. The anti-CD74 humanized monoclonal antibody, milatuzumab, which targets the invariant chain of MHC II complexes, alters B-cell proliferation, migration, and adhesion molecule expression. Arthritis Res. Ther. 2012, 14, R54.
99. Hassan, R.; Bullock, S.; Premkumar, A.; Kreitman R.J.; Kindler, H.; Willingham, M.C.; Pastan, I. Phase I study of SS1P, a recombinant anti-mesothelin immunotoxin given as a bolus i.v. infusion to patients with mesothelin-expressing mesothelioma, ovarian, and pancreatic cancers. Clin. Cancer Res. 2007, 13, 5144-5149.
100. Kreitman, R.J.; Hassan, R.; Fitzgerald, D.J.; Pastan, I. Phase I trial of continuous infusion anti-mesothelin recombinant immunotoxin SS1P. Clin. Cancer Res. 2009, 15, 5274-5279.
101. Hassan, R.; Cohen, S.J.; Phillips, M.; Pastan, I.; Sharon, E.; Kelly R.J.; Schweizer, C.; Weil, S.; Laheru, D. Phase I clinical trial of the chimeric anti-mesothelin monoclonal antibody MORAb-009 in patients with mesothelin-expressing cancers. Clin. Cancer Res. 2010, 16, 6132-6138.
102. Le, D. Results of phase I studies testing twolive-attenuated Listeria vaccines, ANZ-100 and CrS-207, for the treatment of cancer. Presented at the AACR Conference, Tumor Immunology: Basic and Clinical Advances, Miami Beach, FL, USA, Nov 30-Dec 3, 2010; Abstract No. B12.
103. Phase I Study to Determine the Maximum Tolerable Dose of BAY94-9343 in Patients With Advanced Solid Tumors. ClinicalTrials. gov Identifier: NCT01439152. Available online: http://www.clinicaltrials.gov/ct2/show/NCT01439152?term=NCT01439152&rank=1 (accessed on 28 November 2012).
104. Mamot, C; Ritschard R.; Wicki, A.; Stehle, G.; Dieterle, T.; Bubendorf, L.; Hilker, C.; Dester, S.; Herrmann, R.; Rochlitz, C. Tolerability, safety, pharmacokinetics, and efficacy of doxorubicin-loaded anti-EGFR immunoliposomes in advanced solid tumours: A phase 1 dose-escalation study. Lancet Oncol. 2012, doi:10.1016/S1470-2045(12)70476-X.
105. Matsumura, Y.; Gotoh, M.; Muro, K.; Yamada, Y.; Shirao, K.; Shimada, Y.; Okuwa, M.; Matsumoto, S.; Miyata, Y.; Ohkura, H. Phase I and pharmacokinetic study of MCC-465, a doxorubicin (DXR) encapsulated in PEG immunoliposome, in patients with metastatic stomach cancer. Ann. Oncol. 2004, 15, 517-525.
106. Kreitman, R.J.; Tallman, M.S.; Robak, T.; Coutre, S.; Wilson W.H.; Stetler-Stevenson, M.; Fitzgerald, D.J.; Lechleider, R.; Pastan, I. Phase I trial of anti-CD22 recombinant immunotoxin moxetumomab pasudotox (CAT-8015 or HA22) in patients with hairy cell leukemia. J. Clin. Oncol. 2012, 30, 1822-1828.
107. Kowalski, M.; Entwistle, J.; Cizeau, J.; Niforos, D.; Loewen, S.; Chapman, W.; MacDonald, G.C. A Phase I study of an intravesically administered immunotoxin targeting EpCAM for the treatment of nonmuscle-invasive bladder cancer in BCGrefractory and BCG-intolerant patients. Drug Des. Devel. Ther. 2010, 4, 313-320.
108. Garland, L.; Gitlitz, B.; Ebbinghaus, S.; Pan, H.; da Haan, H.; Puri, R.K.; von Hoff, D.; Figlin R. Phase I trial of intravenous IL-4 pseudomonas exotoxin protein (NBI-3001) in patients with advanced solid tumors that express the IL-4 receptor. J. Immunother. 2005, 28, 376-381.
109. Kunwar, S. Convection enhanced delivery of IL13-PE38QQR for treatment of recurrent malignant glioma: Presentation of interim findings from ongoing phase 1 studies. Acta Neurochir. Suppl. 2003, 88, 105-111.
110. Posey, J.A.; Khazaeli, M.B.; Bookman, M.A.; Nowrouzi, A.; Grizzle, W.E.; Thornton, J.; Carey, D.E.; Lorenz, J.M., Sing A.P.; Siegall, C.B.; et al. A phase I trial of the single-chain immunotoxin SGN-10 (BR96 sFv-PE40) in patients with advanced solid tumors. Clin. Cancer Res. 2002, 8, 3092-3099.
111. MacDonald, G.C.; Rasamoelisolo, M.; Entwistle, J.; Cuthbert, W.; Kowalski, M.; Spearman, M.A.; Glover, N. A phase I clinical study of intratumorally administered VB4-845, an anti-epithelial cell adhesion molecule recombinant fusion protein, in patients with squamous cell carcinoma of the head and neck. Med. Oncol. 2009, 26, 257-264.
112. Krop, I.E.; Beeram, M.; Modi, S.; Jones, S.F.; Holden S.N.; Yu, W.; Girish, S.; Tibbitts, T.; Yi, J.H.; Sliwkowski, M.X. 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. 2010, 28, 2698-2704.
113. LeMaistre, C.F.; Saleh, M.N.; Kuzel, T.M.; Foss, F.; Platanias, L.C.; Schwartz, G.; Ratain, M.; Rook, A.; Freytes, C.O.; Craig, F.; et al. Phase I trial of a ligand fusion-protein (DAB389IL-2) in lymphomas expressing the receptor for interleukin-2. Blood 1998, 91, 399-405.
114. Bartlett, N. Retreatment with brentuximab vedotin in CD30-positive hematologic malignancies: A phase II study. J. Clin. Oncol. 2012, 30(suppl.), abstract 8027.
115. Pro, B.; Advani, R.; Brice, P.; Bartlett, N.L.; Rosenblatt, J.D.; Illidge, T.; Matous, J.; Ramchandren, R.; Fanale, M.; Connors, J.M.; et al. Brentuximab Vedotin (SGN-35) in patients with relapsed or refractory systemic anaplastic large-cell Lymphoma: Results of a phase II Study. J. Clin. Oncol. 2012, 30, 2190-2196.
116. Perez, E. Efficacy and safety of Trastuzumab-DM1 vs. Trastuzumab plus Docetaxel in HER-2-positive metastatic breast cancer patients with no prior chemotherapy for metastatic disease: Preliminary results of a randomizes, multicenter, open-label phase 2 study (TDM4). Presented at the ESMO 2010, Chicago, USA, 2010; Abstract LBA 3.
117. Pollack, V.A.; Alvarez, E.; Tse, K.F.; Torgov, M.Y.; Xie, S.; Shenoy, S.G.; MacDougall, J.R.; Arrol, S.; Zhong, H.; Gerwien, R.W.; et al. Treatment parameters modulating regression of human melanoma xenografts of an antibody-drug conjugate (CR011-vcMMAE) targeting GPNMB. Cancer Chemother. Pharmacol. 2007, 60, 423-435.
118. Sznol, M. Phase I pharmacokinetic study of CR011-vcMMAE, an antibody toxin conjugate drug, in patients with unresectable stage III/IV melanoma. Presented at the AACR-NCI-EORTC Conference on Molecular Targets and Cancer Therapeutics, San Francisco, CA, USA, 2007; Abstract B47.
119. Burris, H. A phase I/II study of CRO11-vcMMAE (CDX-011), an antibody-drug conjugate, in patients with locally advances or metastatic breast cancer. Presented at the 32nd Annual San Antonio Breast Cancer Symposium; San Antonio, TX, USA, 2009; Abstract 6096.
120. Hwu, P. A phase I/II study of CR011-vcMMAE, an antibody-drug conjugate (ADC) targeting glycoprotein NMB (GPNMB) in patients (pts) with advanced melanoma. J. Clin. Oncol. 2009, 27(15S), abstract 9032.
121. Mita, M. A phase I study of a CanAg-targeted immunoconjugate, huC242-DM4, in patients with Can Ag-expressing solid tumors. J. Clin. Oncol. 2007, 25(18S), Abstract 3062.
122. Fidias, P.; Grossbard, M.; Lynch, T.J., Jr. A phase II study of the immunotoxin N901-blocked ricin in small-cell lung cancer. Clin. Lung Cancer 2002, 3, 219-222.
123. Kantarjian, H.; Thomas, D.; Jorgensen, J.; Jabbour, E.; Kebriaei, P.; Ritting, M.; York, S.; Ravandi, F.; Kwari, M.; Faderl, S.; et al. Inotuzumab ozogamicin, an anti-CD22-calecheamicin conjugate, for refractory and relapsed acute lymphocytic leukaemia: A phase 2 study. Lancet Oncol. 2012, 13, 403-411.
124. Chen, R.; Results of a pivotal Phase 2 study of brentuximab vedotin (SGN-35) in patients with relapsed or refractory Hodgkin lymphoma. Blood 2010, 116(21), Abstract 283.
125. Shustov, A. Complete remissions with brentuximab vedotin (SGN-35) in patients with relapsed or refractory systemic anaplastic large cell lymphoma. Blood 2010, 116(21), Abstract 961.
126. ImmunoGen, Inc. Press release: ImmunoGen reports fourth quarter and fiscal year 2004 financial results; revenue from partners increased substantially over 2003 levels. Available online: http://investor.immunogen.com/releasedetail.cfm?ReleaseID=649263 (accessed on 23 November 2012).
127. Younes, A.; Gopal, A.K.; Smith, S.E.; Ansell, S.M.; Rosenblatt, J.D.; Savage, K.J.; Ramchandren, R.; Bartlett, N.L.; Cheson, B.D.; de Vos, S.; et al. Results of a pivotal phase II study of Brentuximab Vedotin for patients with relapsed or refractory Hodgkin's Lymphoma. J. Clin. Oncol. 2012, 30, 2183-2189.
128. Burris, H.A., 3rd; Rugo, H.S.; Vukelja, S.J.; Vogel, C.L.; Borson, R.A.; Limantani, S.; Tan-Chiu, E.; Krop, I.E.; Michaelson, R.A.; Girish, S.; et al. 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. 2011, 29, 398-405.
129. Kreitman, R.J.; Stetler-Stevenson, M.; Margulies, I.; Noel, P.; Fitzgerlad, D.J.; Wilson, W.H.; Pastan, I. Phase II trial of recombinant immunotoxin RFB4(dsFv)-PE38 (BL22) in patients with hairy cell leukemia. J. Clin. Oncol. 2009, 27, 2983-2990.
130. Amadori, S.; Suciu, S.; Stasi, R.; Willemze, R.; Mandelli, F.; Selleslag, D.; Denzlinger, C.; Muus, P.; Stauder, R.; Berneman, Z.; et al. Gemtuzumab ozogamicin (Mylotarg) as single-agent treatment for frail patients 61 years of age and older with acute myeloid leukemia: final results of AML-15B, a phase 2 study of the European Organisation for Research and Treatment of Cancer and Gruppo Italiano Malattie Ematologiche dell'Adulto Leukemia Groups. Leukemia 2005, 19, 1768-1773.
131. Tolcher, A.W.; Sugarman, S.; Gelmon, K.A.; Cohen, R.; Saleh, M.; Isaacs, C.; Healey, D.; Onetto, N.; Slichemyer, W. Randomized phase II study of BR96-doxorubicin conjugate in patients with metastatic breast cancer. J. Clin. Oncol. 1999, 17, 478-484.
132. Multani, P.S.; O'Day, S.; Nadler, L.M.; Grossbard, M.L. Phase II clinical trial of bolus infusion anti-B4 blocked ricin immunoconjugate in patients with relapsed B-cell non-Hodgkin's lymphoma. Clin. Cancer Res. 1998, 4, 2599-2604.
133. Grossbard, M.L.; Fidias, P.; Kinsella, J.; O'Toole, J.; Lambert, J.M.; Blattler, W.A.; Esseltine, D.; Braman, G.; Nadler, L.M.; Anderson, K.C. Anti-B4-blocked ricin: A phase II trial of 7 day continuous infusion in patients with multiple myeloma. Br. J. Haematol. 1998, 102, 509-515.
134. Krop, I. A phase 2 study of the HER2 antibody-drug conjugate trastuzumab-DM1 (T-DM1) in patients (pts) with HER2-positive metastatic breast cancer (MBC) previously treated with trastuzumab, lapatinib, and chemotherapy. Presented at the ESMO 2010, Milan, Italy, 2010; Abstract 5082.
135. Telang, S.; Rasku, M.A.; Clem, A. L; Carter, K.; Klarer, A.C.; Badger, W.R.; Milam, R.A.; Rai, S.N.; Pan. J.; Gragg, H.; et al. Phase II trial of the regulatory T cell-depleting agent, denileukin diftitox, in patients with unresectable stage IV melanoma. BMC Cancer 2011, 11, 515.
136. Gerena-Lewis, M.; Crawford, J.; Bonomi, P.; Maddox, A.M.; Hainsworth, J.; McCune, D.E.; Shukla, R.; Zeigler, H.; Hurtubise, P.; Chowdhury, T.R.; et al. A Phase II trial of Denileukin Diftitox in patients with previously treated advanced non-small cell lung cancer. Am. J. Clin. Oncol. 2009, 32, 269-273.
137. Kuzel, T.M.; Li, S.; Eklund, J.; Foss, F.; Gascoyne, R.; Abramson, N.; Schwerkoske, J.F.; Weller, E.; Horning, S.J. Phase II study of denileukin diftitox for previously treated indolent non-Hodgkin lymphoma: Final results of E1497. Leuk. Lymphoma 2007, 48, 2397-2402.
138. Dang, N.H.; Pro, B.; Hagemeister, F.B.; Samaniego, F.; Jones, D.; Samuels, B.I.; Rodriguez, M.A.; Goy, A.; Romaguera, J.E.; McLaughlin, P.; et al. Phase II trial of denileukin diftitox for relapsed/refractory T-cell non-Hodgkin lymphoma. Br. J. Haematol. 2007, 136, 439-447.
139. Frankel, A.E.; Surendranathan, A.; Black, J.H.; White, A.; Ganjoo, K.; Cripe, L.D. Phase II clinical studies of denileukin diftitox diphtheria toxin fusion protein in patients with previously treated chronic lymphocytic leukemia. Cancer 2006, 106, 2158-2164.
140. Dang, N.H.; Hagemeister, F.B.; Pro, B.; McLaughlin, P.; Romaguera, J.E.; Jones, D.; Samuels, B.; Smaniego, F.; Younes, F.; Wang, M.; et al. Phase II study of denileukin diftitox for relapsed/refractory B-Cell non-Hodgkin's lymphoma. J. Clin. Oncol. 2004, 22, 4095-4102.
141. Frankel, A.E.; Fleming, D.R.; Hall, P.D.; Powell, B.L.; Black, J.H.; Leftwich, C.; Gartenhaus, R. A phase II study of DT fusion protein denileukin diftitox in patients with fludarabine-refractory chronic lymphocytic leukemia. Clin. Cancer Res. 2003, 9, 3555-3561.
142. Blackwell, K. Primary results from EMILIA, a phase III study of trastuzumab emtansine (T-DM1) versus capecitabine (X) and lapatinib (L) in HER2-positive locally advanced or metastatic breast cancer (MBC) previously treated with trastuzumab (T) and a taxane. J. Clin. Oncol. 2012, 30(suppl), abstr LBA1.
143. LoRusso, P.M.; Weiss, D.; Guardino, E.; Girish, S.; Sliwkowski, M.X. Trastuzumab emtansine: A unique antibody-drug conjugate in development for human epidermal growth factor receptor 2-positive cancer. Clin. Cancer Res. 2011, 17, 6437-6447.
144. Verma, S.; Miles, D.; Gianni, L.; Krop, I.E.; Welslau, M.; Baselga, M.; Pegram, M.; Oh, D.Y.; Dieras, V.; Guardino, E.; et al. Trastuzumab emtansine for HER2-positive advanced breast cancer. N. Engl. J. Med. 2012, 367, 1783-1791.
145. Ellis, P. MARIANNE: A phase III, randomized study of trastuzumab-DM1 (T-DM1) with or without pertuzumab (P) compared with trastuzumab (H) plus taxane for first-line treatment of HER2-positive, progressive, or recurrent locally advanced or metastatic breast cancer (MBC). J. Clin. Oncol. 2011, 29(suppl), Abstract TPS102.
146. The AETHERA Trial: A randomized, double-blind, placebo-controlled phase 3 Study of SGN-35 and Best Supportive Care (BSC) versus placebo and BSC in the treatment of patients at high risk of residual Hodgkin lymphoma following autologous stem cell transplant. ClinicalTrials. gov identifier: NCT01100502. Available online: http://www.clinicaltrials.gov/ct2/show/NCT011 00502?term=NCT01100502&rank=1 (accessed on 28 November 2012).
147. Lowenberg, B.; Beck, J.; Graux, C.; van Putten, W.; Schouten, H.C.; Verdonck, L.F., Ferrant, A.; Sonneveld. P.; Jongen-Lavrencic, M.; von Lilienfeld-Toar, M.; et al. Gemtuzumab ozogamicin as postremission treatment in AML at 60 years of age or more: results of a multicenter phase 3 study. Blood 2010, 115, 2586-2591.
148. Castaigne, S.; Pautas, C.; Terre, C.; Raffoux, E.; Bordessoule, D.; Bastie, J.N.; Legrand, O.; Thomas, X.; Turlure, P.; Reman, O; et al. Effect of gemtuzumab ozogamicin on survival of adult patients with de novo acute myeloid leukaemia (ALFA-0701): A randomised, open-label, phase 3 study. Lancet 2012, 379, 1508-1516.
149. INO-VATE ALL STUDY 1022: A phase 3 study of Inotuzumab Ozogamicin versus investigator's choice of chemotherapy in patients with relapsed or refractory acute Lymphoblastic Leukemia. Clinicaltrials. gov. Identifier: NCT01564784. Available online: http://www.clinicaltrials.gov/ct2/show/NCT01564784?term=inotuzumab&rank=7 (accessed on 28 November 2012).
150. Furman, R.R.; Grossbard, M.L.; Johnson, J.L.; Pecora, A.L.; Cassileth, P.A.; Jung, S.H.; Peterson, B.A.; Nadler, L.M.; Freedmann, A.; Bayer, R.L.; et al. A phase III study of anti-B4-blocked ricin as adjuvant therapy post-autologous bone marrow transplant: CALGB 9254 Leuk. Lymphoma 2011, 52, 587-596.
151. Prince, H.M.; Duvic, M.; Martin, A.; Sterry, W.; Assaf, C.; Sun, Y.; Straus, D.; Acosta, M.; Negro-Vilar, A. Phase III placebo-controlled trial of denileukin diftitox for patients with cutaneous T-cell lymphoma. J. Clin. Oncol. 2010, 28, 1870-1877.
152. Bartlett, N.L.; Niedzwiecki, D.; Johnson, J.L.; Friedberg, J.W.; Johnson, K.B.; van Besien, K.; Zelenetz, A.D.; Cheson, B.D.; Canellos, G.P. Gemcitabine, vinorelbine, and pegylated liposomal doxorubicin (GVD), a salvage regimen in relapsed Hodgkin's lymphoma: CALGB 59804. Ann. Oncol. 2007, 18, 1071-1079.
153. Duvic, M.; Cather, J.; Maize, J.; Frankel, A.E. DAB389IL2 diphtheria fusion toxin produces clinical responses in tumor stage cutaneous T cell lymphoma. Am. J. Hematol. 1998, 58, 87-90.
154. Lansigan, F.; Stearns, D.M.; Foss, F. Role of denileukin diftitox in the treatment of persistent or recurrent cutaneous T-cell lymphoma. Cancer Manag. Res. 2010, 2, 53-59.
155. Schmidt, S.R. Fusion-proteins as biopharmaceuticals--applications and challenges. Curr. Opin. Drug Discov. Devel. 2009, 12, 284-295.