Antibody drug conjugates for treatment of breast cancer: Novel targets and diverse approaches in ADC design

Pharmacology and Therapeutics

Volumn 181, Issue , 2018, Pages 126-142

  Trail, Pamela A ^a   Dubowchik, Gene M ^b   Lowinger, Timothy B ^c  

^a REGENERON PHARMACEUTICALS INC   (United States)

^b BRISTOL MYERS SQUIBB   (United States)

^c Mersana Therapeutics Inc   (United States)

Author keywords

Antibody drug conjugate; Antibody directed delivery; Breast cancer; Cancer therapy; Immunoconjugate; Monoclonal antibody

Indexed keywords

ADCT 502; ANTIBODY DRUG CONJUGATE; ANTINEOPLASTIC AGENT; ARX 788; DS 8201A; EPHRIN A4; EPIDERMAL GROWTH FACTOR RECEPTOR 2; GLEMBATUMUMAB VEDOTIN; LIV 1 PROTEIN; LYSOSOMAL MEMBRANE ASSOCIATE PROTEIN 1; MEDI 4276; MEMBRANE PROTEIN; P CADHERIN; PROTEIN; PROTEIN TYROSINE KINASE; PROTEIN TYROSINE KINASE 7; PROTEIN TYROSINE KINASE INHIBITOR; SACITUZUMAB GOVITECAN; SAR 566658; TRASTUZUMAB DUOCARMAZINE; TRASTUZUMAB EMTANSINE; UNCLASSIFIED DRUG; XMT 1522; ANTIBODY CONJUGATE; MONOCLONAL ANTIBODY;

BREAST CANCER; CANCER IMMUNOTHERAPY; DRUG DESIGN; LYSOSOME MEMBRANE; MOLECULARLY TARGETED THERAPY; PRIORITY JOURNAL; REVIEW; BREAST TUMOR; HUMAN; PROCEDURES;

ANTIBODIES, MONOCLONAL, HUMANIZED; BREAST NEOPLASMS; HUMANS; IMMUNOCONJUGATES; MOLECULAR TARGETED THERAPY;

EID: 85026759386     PISSN: 01637258     EISSN: 1879016X     Source Type: Journal    
DOI: 10.1016/j.pharmthera.2017.07.013     Document Type: Review

References (103)

1. Adem, Y.T., Schwarz, K.A., Duenas, E., Patapoff, T.W., Galush, W.J., Esue, O., Auristatin antibody drug conjugate physical instability and the role of drug payload. Bioconjugate Chemistry 25:4 (2014), 656–664.
2. Agarwal, N., Machiels, J.P., Suarez, C., Lewis, N., Higgins, M., Wisinski, K., Elmeliegy, M., Phase I study of the prolactin receptor antagonist LFA102 in metastatic breast and castration-resistant prostate cancer. The Oncologist 21:5 (2016), 535–536.
3. Alter, G., Malenfant, J.M., Altfeld, M., CD107a as a functional marker for the identification of natural killer cell activity. Journal of Immunological Methods 294:1–2 (2004), 15–22.
4. Amiri-Kordestani, L., Blumenthal, G.M., Xu, Q.C., Zhang, L., Tang, S.W., Ha, L., Cortazar, P., FDA approval: Ado-trastuzumab emtansine for the treatment of patients with HER2-positive metastatic breast cancer. Clinical Cancer Research 20:17 (2014), 4436–4441.
5. Ataseven, B., Angerer, R., Kates, R., Gunesch, A., Knyazev, P., Hogel, B., Harbeck, N., PTK7 expression in triple-negative breast cancer. Anticancer Research 33:9 (2013), 3759–3763.
6. Bardia, A., Mayer, I.A., Diamond, J.R., Moroose, R.L., Isakoff, S.J., Starodub, A.N., Vahdat, L.T., Efficacy and safety of anti-Trop-2 antibody drug conjugate sacituzumab govitecan (IMMU-132) in heavily pretreated patients with metastatic triple-negative breast cancer. Journal of Clinical Oncology, 2017 (Jco2016708297. Retrieved from).
7. Baselga, J., Treatment of HER2-overexpressing breast cancer. Annals of Oncology 21:Suppl. 7 (2010), vii36–40.
8. Baudat, Y., Cameron, B., Dabdoubi, T., Lefebvre, A.-M., Merino-Trigo, A., Thomas, C., Blanc, V., Abstract 1198: characterization of a novel maytansinoid-antibody-drug conjugate targeting LAMP1 expressed at the surface of tumor cells. Proceedings of the 107th annual meeting of the American Association for Cancer Research, New Orleans, LA, 2016.
9. Bendell, J., Saleh, M., Rose, A.A., Siegel, P.M., Hart, L., Sirpal, S., Vahdat, L., Phase I/II study of the antibody-drug conjugate glembatumumab vedotin in patients with locally advanced or metastatic breast cancer. Journal of Clinical Oncology 32:32 (2014), 3619–3625.
10. Boni, V., Rixe, O., Rasco, D., Gomez-Roca, C., Calvo, E., Morris, J.C., Delord, J.-P., Abstract A73: A phase I first-in-human (FIH) study of SAR566658, an anti CA6-antibody drug conjugate (ADC), in patients (pts) with CA6-positive advanced solid tumors (STs). Proceedings of the AACR-NCI-EORTC international conference: Molecular targets and cancer therapeutics; 2013 Boston, MA, 2013.
11. Boonstra, M.C., de Geus, S.W., Prevoo, H.A., Hawinkels, L.J., van de Velde, C.J., Kuppen, P.J., Sier, C.F., Selecting targets for tumor imaging: An overview of cancer-associated membrane proteins. Biomark Cancer 8 (2016), 119–133.
12. Burris, H.A. 3rd, Tibbitts, J., Holden, S.N., Sliwkowski, M.X., Lewis Phillips, G.D., Trastuzumab emtansine (T-DM1): A novel agent for targeting HER2 + breast cancer. Clinical Breast Cancer 11:5 (2011), 275–282.
13. Calvet, L., Lefebvre, A.-M., Nicolazzi, C., Blot, L., Thomas, C., Baudat, Y., Sidhu, S., Abstract 1197: Outstanding preclinical efficacy of a novel maytansinoid-antibody-drug conjugate targeting LAMP1 in patient-derived xenograft solid tumors. Proceedings: AACR 107th annual meeting, New Orleans, LA, 2016.
14. Cardillo, T.M., Govindan, S.V., Sharkey, R.M., Trisal, P., Goldenberg, D.M., Humanized anti-Trop-2 IgG-SN-38 conjugate for effective treatment of diverse epithelial cancers: Preclinical studies in human cancer xenograft models and monkeys. Clinical Cancer Research 17:10 (2011), 3157–3169.
15. Carl, P.L., Chakravarty, P.K., Katzenellenbogen, J.A., A novel connector linkage applicable in prodrug design. Journal of Medicinal Chemistry 24:5 (1981), 479–480.
16. Chari, R.V., Targeted cancer therapy: Conferring specificity to cytotoxic drugs. Accounts of Chemical Research 41:1 (2008), 98–107.
17. Chen, R., Khatri, P., Mazur, P.K., Polin, M., Zheng, Y., Vaka, D., Sweet-Cordero, E.A., A meta-analysis of lung cancer gene expression identifies PTK7 as a survival gene in lung adenocarcinoma. Cancer Research 74:10 (2014), 2892–2902.
18. Constantinou, P.E., Danysh, B.P., Dharmaraj, N., Carson, D.D., Transmembrane mucins as novel therapeutic targets. Expert Review of Endocrinology and Metabolism 6:6 (2011), 835–848.
19. Damelin, M., Bankovich, A., Bernstein, J., Lucas, J., Chen, L., Williams, S., Dylla, S.J., A PTK7-targeted antibody-drug conjugate reduces tumor-initiating cells and induces sustained tumor regressions. Science Translational Medicine, 9(372), 2017.
20. Damelin, M., Bankovich, A., Park, A., Aguilar, J., Anderson, W., Santaguida, M., Dylla, S.J., Anti-EFNA4 calicheamicin conjugates effectively target triple-negative breast and ovarian tumor-initiating cells to result in sustained tumor regressions. Clinical Cancer Research 21:18 (2015), 4165–4173.
21. Dokter, W., Ubink, R., van der Lee, M., van der Vleuten, M., van Achterberg, T., Jacobs, D., Timmers, M., Preclinical profile of the HER2-targeting ADC SYD983/SYD985: Introduction of a new duocarmycin-based linker-drug platform. Molecular Cancer Therapeutics 13:11 (2014), 2618–2629.
22. Doronina, S.O., Toki, B.E., Torgov, M.Y., Mendelsohn, B.A., Cerveny, C.G., Chace, D.F., Senter, P.D., Development of potent monoclonal antibody auristatin conjugates for cancer therapy. Nature Biotechnology 21:7 (2003), 778–784.
23. Dubowchik, G.M., Firestone, R.A., Padilla, L., Willner, D., Hofstead, S.J., Mosure, K., Trail, P.A., Cathepsin B-labile dipeptide linkers for lysosomal release of doxorubicin from internalizing immunoconjugates: Model studies of enzymatic drug release and antigen-specific in vitro anticancer activity. Bioconjugate Chemistry 13:4 (2002), 855–869.
24. Elgersma, R.C., Coumans, R.G., Huijbregts, T., Menge, W.M., Joosten, J.A., Spijker, H.J., Beusker, P.H., Design, synthesis, and evaluation of linker-duocarmycin payloads: Toward selection of HER2-targeting antibody-drug conjugate SYD985. Molecular Pharmaceutics 12:6 (2015), 1813–1835.
25. El-Tanani, M.K., Green, C.D., Interaction between estradiol and growth factors in the regulation of specific gene expression in MCF-7 human breast cancer cells. The Journal of Steroid Biochemistry and Molecular Biology 60:5–6 (1997), 269–276.
26. Eskelinen, E.L., Roles of LAMP-1 and LAMP-2 in lysosome biogenesis and autophagy. Molecular Aspects of Medicine 27:5–6 (2006), 495–502.
27. Fauteux, F., Hill, J.J., Jaramillo, M.L., Pan, Y., Phan, S., Famili, F., O'Connor-McCourt, M., Computational selection of antibody-drug conjugate targets for breast cancer. Oncotarget 7:3 (2016), 2555–2571.
28. Ghosh, N., Sheldrake, H.M., Searcey, M., Pors, K., Chemical and biological explorations of the family of CC-1065 and the duocarmycin natural products. Current Topics in Medicinal Chemistry 9:16 (2009), 1494–1524.
29. Giaginis, C., Tsoukalas, N., Bournakis, E., Alexandrou, P., Kavantzas, N., Patsouris, E., Theocharis, S., Ephrin (Eph) receptor A1, A4, A5 and A7 expression in human non-small cell lung carcinoma: Associations with clinicopathological parameters, tumor proliferative capacity and patients' survival. BMC Clinical Pathology, 14(1), 2014, 8.
30. de Goeij, B.E., Lambert, J.M., New developments for antibody-drug conjugate-based therapeutic approaches. Current Opinion in Immunology 40 (2016), 14–23.
31. Goldenberg, D.M., Cardillo, T.M., Govindan, S.V., Rossi, E.A., Sharkey, R.M., Trop-2 is a novel target for solid cancer therapy with sacituzumab govitecan (IMMU-132), an antibody-drug conjugate (ADC). Oncotarget 6:26 (2015), 22496–22512.
32. Gomez-Roca, C., V, B., V, M., JC, M., J-P, D., E, C., AW, T., A phase I study of SAR566658, an anti CA6-antibody drug conjugate (ADC), in patients (pts) with CA6-positive advanced solid tumors (STs)(NCT01156870). Molecular targets and cancer therapeutics, Boston, MA, 2016.
33. Grattan, B.J., Freake, H.C., Zinc and cancer: Implications for LIV-1 in breast cancer. Nutrients 4:7 (2012), 648–675.
34. Hamann, P.R., Hinman, L.M., Hollander, I., Beyer, C.F., Lindh, D., Holcomb, R., Bernstein, I., Gemtuzumab ozogamicin, a potent and selective anti-CD33 antibody-calicheamicin conjugate for treatment of acute myeloid leukemia. Bioconjugate Chemistry 13:1 (2002), 47–58.
35. Hamblett, K.J., Senter, P.D., Chace, D.F., Sun, M.M., Lenox, J., Cerveny, C.G., Francisco, J.A., Effects of drug loading on the antitumor activity of a monoclonal antibody drug conjugate. Clinical Cancer Research 10:20 (2004), 7063–7070.
36. Humphreys, R.C., Kirtely, J., Hewit, A., Biroc, S., Knudsen, N., Skidmore, L., Wahl, A., Abstract 639: Site specific conjugation of ARX-788, an antibody drug conjugate (ADC) targeting HER2, generates a potent and stable targeted therapeutic for multiple cancers. Proceedings of the 106th annual meeting of the American Association for Cancer Research, Philadelphia, PA, 2015.
37. Jeffrey, S.C., Burke, P.J., Lyon, R.P., Meyer, D.W., Sussman, D., Anderson, M., Senter, P.D., A potent anti-CD70 antibody-drug conjugate combining a dimeric pyrrolobenzodiazepine drug with site-specific conjugation technology. Bioconjugate Chemistry 24:7 (2013), 1256–1263.
38. Kasper, G., Weiser, A.A., Rump, A., Sparbier, K., Dahl, E., Hartmann, A., Lehmann, K., Expression levels of the putative zinc transporter LIV-1 are associated with a better outcome of breast cancer patients. International Journal of Cancer 117:6 (2005), 961–973.
39. Katz, J., Janik, J.E., Younes, A., Brentuximab vedotin (SGN-35). Clinical Cancer Research 17:20 (2011), 6428–6436.
40. Klute, K., Nackos, E., Tasaki, S., Nguyen, D.P., Bander, N.H., Tagawa, S.T., Microtubule inhibitor-based antibody-drug conjugates for cancer therapy. OncoTargets and Therapy 7 (2014), 2227–2236.
41. Kovtun, Y.V., Goldmacher, V.S., Cell killing by antibody-drug conjugates. Cancer Letters 255:2 (2007), 232–240.
42. Lambert, J.M., Morris, C.Q., Antibody–drug conjugates (ADCs) for personalized treatment of solid tumors: A review. Advances in Therapy 34:5 (2017), 1015–1035.
43. van der Lee, M.M., Groothuis, P.G., Ubink, R., van der Vleuten, M.A., van Achterberg, T.A., Loosveld, E.M., Dokter, W.H., The preclinical profile of the duocarmycin-based HER2-targeting ADC SYD985 predicts for clinical benefit in low HER2-expressing breast cancers. Molecular Cancer Therapeutics 14:3 (2015), 692–703.
44. Lewis Phillips, G.D., Li, G., Dugger, D.L., Crocker, L.M., Parsons, K.L., Mai, E., Sliwkowski, M.X., Targeting HER2-positive breast cancer with trastuzumab-DM1, an antibody-cytotoxic drug conjugate. Cancer Research 68:22 (2008), 9280–9290.
45. Li, D.M., Feng, Y.M., Signaling mechanism of cell adhesion molecules in breast cancer metastasis: Potential therapeutic targets. Breast Cancer Research and Treatment 128:1 (2011), 7–21.
46. Li, J.Y., Perry, S.R., Muniz-Medina, V., Wang, X., Wetzel, L.K., Rebelatto, M.C., Coats, S.R., A biparatopic HER2-targeting antibody-drug conjugate induces tumor regression in primary models refractory to or ineligible for HER2-targeted therapy. Cancer Cell 29:1 (2016), 117–129.
47. Liu, C., Huang, H., Wang, C., Kong, Y., Zhang, H., Involvement of ephrin receptor A4 in pancreatic cancer cell motility and invasion. Oncology Letters 7:6 (2014), 2165–2169.
48. Lu, M., Zhu, H., Wang, X., Zhang, D., Xiong, L., Zhu, J., Qiang, J., LAMP1 expression is associated with malignant behaviours and predicts unfavourable prognosis in laryngeal squamous cell carcinoma. Pathology 48:7 (2016), 684–690.
49. Lyon, R.P., Meyer, D.L., Setter, J.R., Senter, P.D., Conjugation of anticancer drugs through endogenous monoclonal antibody cysteine residues. Methods in Enzymology 502 (2012), 123–138.
50. Ma, X., Ma, Q., Liu, J., Tian, Y., Wang, B., Taylor, K.M., Zhou, J., Identification of LIV1, a putative zinc transporter gene responsible for HDACi-induced apoptosis, using a functional gene screen approach. Molecular Cancer Therapeutics 8:11 (2009), 3108–3116.
51. MacMillan, K.S., Boger, D.L., Fundamental relationships between structure, reactivity, and biological activity for the duocarmycins and CC-1065. Journal of Medicinal Chemistry 52:19 (2009), 5771–5780.
52. Maderna, A., Doroski, M., Subramanyam, C., Porte, A., Leverett, C.A., Vetelino, B.C., O'Donnell, C.J., Discovery of cytotoxic dolastatin 10 analogues with N-terminal modifications. Journal of Medicinal Chemistry 57:24 (2014), 10527–10543.
53. Maric, G., Annis, M.G., Dong, Z., Rose, A.A., Ng, S., Perkins, D., Siegel, P.M., GPNMB cooperates with neuropilin-1 to promote mammary tumor growth and engages integrin alpha5beta1 for efficient breast cancer metastasis. Oncogene 34:43 (2015), 5494–5504.
54. Maric, G., Rose, A.A., Annis, M.G., Siegel, P.M., Glycoprotein non-metastatic b (GPNMB): A metastatic mediator and emerging therapeutic target in cancer. OncoTargets and Therapy 6 (2013), 839–852.
55. Martino, E., Della Volpe, S., Terribile, E., Benetti, E., Sakaj, M., Centamore, A., Collina, S., The long story of camptothecin: From traditional medicine to drugs. Bioorganic & Medicinal Chemistry Letters 27:4 (2017), 701–707.
56. Meister, A., Anderson, M.E., Glutathione. Annual Review of Biochemistry 52 (1983), 711–760.
57. Mendelsohn, J., Baselga, J., The EGF receptor family as targets for cancer therapy. Oncogene 19:56 (2000), 6550–6565.
58. Menezes, D., Abrams, T.J., Karim, C., Tang, Y., Ying, C., Miller, K., Damiano, J., Abstract 1682: Development and activity of a novel antibody-drug conjugate for the treatment of P-cadherin expressing cancers. Cancer Research, 75(15 Supplement), 2015, 1682.
59. Mikhail, I., Papisov, A., Hiller, A., Yurkovetskiy, M., Yin, M., Barzana, M., Fischman, A., Semi-synthetic hydrophilic polyals. Biomacromolecules 6 (2005), 2659–2670.
60. Mossie, K., Jallal, B., Alves, F., Sures, I., Plowman, G.D., Ullrich, A., Colon carcinoma kinase-4 defines a new subclass of the receptor tyrosine kinase family. Oncogene 11:10 (1995), 2179–2184.
61. Nakada, T., Masuda, T., Naito, H., Yoshida, M., Ashida, S., Morita, K., Honda, T., Novel antibody drug conjugates containing exatecan derivative-based cytotoxic payloads. Bioorganic & Medicinal Chemistry Letters 26:6 (2016), 1542–1545.
62. Ogitani, Y., Abe, Y., Iguchi, T., Yamaguchi, J., Terauchi, T., Kitamura, M., Agatsuma, T., Wide application of a novel topoisomerase I inhibitor-based drug conjugation technology. Bioorganic & Medicinal Chemistry Letters 26:20 (2016), 5069–5072.
63. Ogitani, Y., Aida, T., Hagihara, K., Yamaguchi, J., Ishii, C., Harada, N., Agatsuma, T., DS-8201a, a novel HER2-targeting ADC with a novel DNA topoisomerase I inhibitor, demonstrates a promising antitumor efficacy with differentiation from T-DM1. Clinical Cancer Research 22:20 (2016), 5097–5108.
64. Ogitani, Y., Hagihara, K., Oitate, M., Naito, H., Agatsuma, T., Bystander killing effect of DS-8201a, a novel anti-human epidermal growth factor receptor 2 antibody-drug conjugate, in tumors with human epidermal growth factor receptor 2 heterogeneity. Cancer Science 107:7 (2016), 1039–1046.
65. Paredes, J., Correia, A.L., Ribeiro, A.S., Milanezi, F., Cameselle-Teijeiro, J., Schmitt, F.C., Breast carcinomas that co-express E- and P-cadherin are associated with p120-catenin cytoplasmic localisation and poor patient survival. Journal of Clinical Pathology 61:7 (2008), 856–862.
66. Patil, P.C., Satam, V., Lee, M., A short review on the synthetic strategies of duocarmycin analogs that are powerful DNA alkylating agents. Anti-Cancer Agents in Medicinal Chemistry 15:5 (2015), 616–630.
67. Rose, A.A., Grosset, A.A., Dong, Z., Russo, C., Macdonald, P.A., Bertos, N.R., Siegel, P.M., Glycoprotein nonmetastatic B is an independent prognostic indicator of recurrence and a novel therapeutic target in breast cancer. Clinical Cancer Research 16:7 (2010), 2147–2156.
68. Roth, M., Barris, D.M., Piperdi, S., Kuo, V., Everts, S., Geller, D., Gorlick, R., Targeting glycoprotein NMB with antibody-drug conjugate, glembatumumab vedotin, for the treatment of osteosarcoma. Pediatric Blood & Cancer 63:1 (2016), 32–38.
69. Saitoh, O., Wang, W.C., Lotan, R., Fukuda, M., Differential glycosylation and cell surface expression of lysosomal membrane glycoproteins in sublines of a human colon cancer exhibiting distinct metastatic potentials. The Journal of Biological Chemistry 267:8 (1992), 5700–5711.
70. Sarafian, V., Jadot, M., Foidart, J.M., Letesson, J.J., Van den Brule, F., Castronovo, V., Coninck, S.W., Expression of Lamp-1 and Lamp-2 and their interactions with galectin-3 in human tumor cells. International Journal of Cancer 75:1 (1998), 105–111.
71. Schumacher, D., Hackenberger, C.P., Leonhardt, H., Helma, J., Current status: Site-specific antibody drug conjugates. Journal of Clinical Immunology 36:Suppl. 1 (2016), 100–107.
72. Senter, P.D., Potent antibody drug conjugates for cancer therapy. Current Opinion in Chemical Biology 13:3 (2009), 235–244.
73. Shvartsur, A., Bonavida, B., Trop2 and its overexpression in cancers: Regulation and clinical/therapeutic implications. Genes & Cancer 6:3–4 (2015), 84–105.
74. Slamon, D., Eiermann, W., Robert, N., Pienkowski, T., Martin, M., Press, M., Crown, J., Adjuvant trastuzumab in HER2-positive breast cancer. The New England Journal of Medicine 365:14 (2011), 1273–1283.
75. Smith, N.L., Halliday, B.E., Finley, J.L., Wennerberg, A.E., The spectrum of immunohistochemical reactivity of monoclonal antibody DS6 in nongynecologic neoplasms. Applied Immunohistochemistry & Molecular Morphology 10:2 (2002), 152–158.
76. Speers, C., Tsimelzon, A., Sexton, K., Herrick, A.M., Gutierrez, C., Culhane, A., Brown, P., Identification of novel kinase targets for the treatment of estrogen receptor-negative breast cancer. Clinical Cancer Research 15:20 (2009), 6327–6340.
77. Stefan, N., Gebleux, R., Waldmeier, L., Hell, T., Escher, M., Wolter, F.I., Beerli, R.R., Highly potent, anthracycline-based antibody-drug conjugates generated by enzymatic, site-specific conjugation. Molecular Cancer Therapeutics, 2017, 879–892.
78. Sussman, D., Smith, L.M., Anderson, M.E., Duniho, S., Hunter, J.H., Kostner, H., Benjamin, D.R., SGN-LIV1A: A novel antibody-drug conjugate targeting LIV-1 for the treatment of metastatic breast cancer. Molecular Cancer Therapeutics 13:12 (2014), 2991–3000.
79. Taylor, K.M., Morgan, H.E., Johnson, A., Hadley, L.J., Nicholson, R.I., Structure-function analysis of LIV-1, the breast cancer-associated protein that belongs to a new subfamily of zinc transporters. The Biochemical Journal 375:Pt 1 (2003), 51–59.
80. Taylor, K.M., Morgan, H.E., Johnson, A., Nicholson, R.I., Structure-function analysis of a novel member of the LIV-1 subfamily of zinc transporters, ZIP14. FEBS Letters 579:2 (2005), 427–432.
81. Taylor, K.M., Morgan, H.E., Smart, K., Zahari, N.M., Pumford, S., Ellis, I.O., Nicholson, R.I., The emerging role of the LIV-1 subfamily of zinc transporters in breast cancer. Molecular Medicine 13:7–8 (2007), 396–406.
82. Thomas, A., Teicher, B.A., Hassan, R., Antibody-drug conjugates for cancer therapy. The Lancet Oncology 17:6 (2016), e254–262.
83. Thompson, P., Fleming, R., Bezabeh, B., Huang, F., Mao, S., Chen, C., Dimasi, N., Rational design, biophysical and biological characterization of site-specific antibody-tubulysin conjugates with improved stability, efficacy and pharmacokinetics. Journal of Controlled Release 236 (2016), 100–116.
84. Tolcher, A.W., Calvo, E., Maitland, M.L., Gibson, B., Xuan, D., Joh, T., Sachdev, J.C., 28LBA A phase 1 study of PF-06647020, an antibody-drug conjugate targeting PTK7, in patients with advanced solid tumors. European Journal of Cancer, 51(Supplement 3), 2015, S724.
85. Trail, P.A., Antibody drug conjugates as cancer therapeutics. Antibodies 2 (2013), 113–129.
86. Trail, P.A., King, H.D., Dubowchik, G.M., Monoclonal antibody drug immunoconjugates for targeted treatment of cancer. Cancer Immunology, Immunotherapy 52:5 (2003), 328–337.
87. Trail, P.A., Willner, D., Lasch, S.J., Henderson, A.J., Hofstead, S., Casazza, A.M., Hellstrom, K.E., Cure of xenografted human carcinomas by BR96-doxorubicin immunoconjugates. Science 261:5118 (1993), 212–215.
88. Turashvili, G., McKinney, S.E., Goktepe, O., Leung, S.C., Huntsman, D.G., Gelmon, K.A., Aparicio, S.A., P-cadherin expression as a prognostic biomarker in a 3992 case tissue microarray series of breast cancer. Modern Pathology 24:1 (2011), 64–81.
89. Unno, J., Masamune, A., Hamada, S., Shimosegawa, T., The zinc transporter LIV-1 is a novel regulator of stemness in pancreatic cancer cells. Scandinavian Journal of Gastroenterology 49:2 (2014), 215–221.
90. Unno, J., Satoh, K., Hirota, M., Kanno, A., Hamada, S., Ito, H., Shimosegawa, T., LIV-1 enhances the aggressive phenotype through the induction of epithelial to mesenchymal transition in human pancreatic carcinoma cells. International Journal of Oncology 35:4 (2009), 813–821.
91. Verma, S., Miles, D., Gianni, L., Krop, I.E., Welslau, M., Baselga, J., Blackwell, K., Trastuzumab emtansine for HER2-positive advanced breast cancer. The New England Journal of Medicine 367:19 (2012), 1783–1791.
92. Vieira, A.F., Paredes, J., P-cadherin and the journey to cancer metastasis. Molecular Cancer, 14, 2015, 178.
93. Walker, S., Landovitz, R., Ding, W.D., Ellestad, G.A., Kahne, D., Cleavage behavior of calicheamicin gamma 1 and calicheamicin T. Proceedings of the National Academy of Sciences of the United States of America 89:10 (1992), 4608–4612.
94. Wethington, S.L., Wright, J.D., Herzog, T.J., Key role of topoisomerase I inhibitors in the treatment of recurrent and refractory epithelial ovarian carcinoma. Expert Review of Anticancer Therapy 8:5 (2008), 819–831.
95. Widdison, W.C., Wilhelm, S.D., Cavanagh, E.E., Whiteman, K.R., Leece, B.A., Kovtun, Y., Chari, R.V., Semisynthetic maytansine analogues for the targeted treatment of cancer. Journal of Medicinal Chemistry 49:14 (2006), 4392–4408.
96. Yarden, Y., Biology of HER2 and its importance in breast cancer. Oncology 61:Suppl. 2 (2001), 1–13.
97. Yardley, D.A., Weaver, R., Melisko, M.E., Saleh, M.N., Arena, F.P., Forero, A., Vahdat, L.T., EMERGE: A randomized phase II study of the antibody-drug conjugate glembatumumab vedotin in advanced glycoprotein NMB-expressing breast cancer. Journal of Clinical Oncology 33:14 (2015), 1609–1619.
98. Younes, A., Novel treatment strategies for patients with relapsed classical Hodgkin lymphoma. Hematology. American Society of Hematology. Education Program, 2009, 507–519.
99. 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. The New England Journal of Medicine 363:19 (2010), 1812–1821.
100. Yurkovetskiy, A., Gumerov, D., Ter-Ovanesyan, E., Conlon, P., Devit, M., Bu, C., Bergstrom, D., Non-clinical pharmacokinetics of XMT-1522, a HER2 targeting auristatin-based antibody drug conjugate. Proceedings of the American Association for Cancer Research, Washington, DC, 2017.
101. Yurkovetskiy, A.V., Yin, M., Bodyak, N., Stevenson, C.A., Thomas, J.D., Hammond, C.E., Lowinger, T.B., A polymer-based antibody–Vinca drug conjugate platform: Characterization and preclinical efficacy. Cancer Research 75:16 (2015), 3365–3372.
102. Zammarchi, F., Chivers, S., Williams, D.G., Adams, L., Mellinas-Gomez, M., Tyrer, P., Van Berkel, P.H., 62 - ADCT-502, a novel pyrrolobenzodiazepine (PBD)-based antibody–drug conjugate (ADC) targeting low HER2-expressing solid cancers. European Journal of Cancer, 69(Supplement 1), 2016, S28.
103. Zeng, P., Chen, M.B., Zhou, L.N., Tang, M., Liu, C.Y., Lu, P.H., Impact of TROP2 expression on prognosis in solid tumors: A systematic review and meta-analysis. Scientific Reports, 6, 2016, 33658.