1932

Abstract

The concept of exploiting the specific binding properties of monoclonal antibodies as a mechanism for selective delivery of cytotoxic agents to tumor cells is an attractive solution to the challenge of increasing the therapeutic index of cell-killing agents for treating cancer. All three parts of an antibody–drug conjugate (ADC)—the antibody, the cytotoxic payload, and the linker chemistry that joins them together—as well as the biologic properties of the cell-surface target antigen are important in designing an effective anticancer agent. The approval of brentuximab vedotin in 2011 for treating relapsed Hodgkin's lymphoma and systemic anaplastic large cell lymphoma, and the approval of ado-trastuzumab emtansine in 2013 for treating HER2-positive metastatic breast cancer, have sparked vigorous research in the field, with >65 ADCs currently in clinical evaluation. This review highlights the ADCs that are approved for marketing, in pivotal clinical trials, or in at least phase II clinical development for treating both hematologic malignancies and solid tumors.

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2018-01-29
2024-03-29
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Literature Cited

  1. Miller DR. 1.  2006. A tribute to Sidney Farber—the father of modern chemotherapy. Br. J. Haematol. 134:20–26 [Google Scholar]
  2. Frei E III. 2.  1972. Combination cancer therapy: presidential address. Cancer Res 32:2593–607 [Google Scholar]
  3. Chari RV, Miller ML, Widdison WC. 3.  2014. Antibody-drug conjugates: an emerging concept in cancer therapy. Angew Chem. Int. Ed. 53:3796–827 [Google Scholar]
  4. Issel BF, Crooke ST. 4.  1978. Maytansine. Cancer Treat. Rev. 5:199–207 [Google Scholar]
  5. Cristofanilli M, Bryan WJ, Miller LL. 5.  et al. 1998. Phase II study of adozelesin in untreated metastatic breast cancer. Anticancer Drugs 9:779–82 [Google Scholar]
  6. Kohler G, Milstein C. 6.  1975. Continuous cultures of fused cells secreting antibody of predefined specificity. Nature 256:495–97 [Google Scholar]
  7. Lambert JM. 7.  2017. Typical antibody-drug conjugates. Antibody-Drug Conjugates: Fundamentals, Drug Development, and Clinical Outcomes to Target Cancer KJ Olivier Jr., SA Hurvitz 3–32 Hoboken, NJ: Wiley [Google Scholar]
  8. Senter PD, Sievers EL. 8.  2012. The discovery and development of brentuximab vedotin for use in relapsed Hodgkin lymphoma and systemic anaplastic large cell lymphoma. Nat. Biotechnol. 30:631–37 [Google Scholar]
  9. Lambert JM, Chari RV. 9.  2014. Ado-trastuzumab emtansine (T-DM1): an antibody-drug conjugate (ADC) for HER2-positive breast cancer. J. Med. Chem 576949–64 [Google Scholar]
  10. Beck A, Goetsch L, Dumontet C. 10.  et al. 2017. Strategies and challenges for the next generation of antibody-drug conjugates. Nat. Rev. Drug Discov. 16:315–37 [Google Scholar]
  11. Starling JJ, Maciak RS, Law KL. 11.  et al. 1991. In vivo antitumor activity of a monoclonal antibody-vinca alkaloid immunoconjugate directed against a solid tumor membrane antigen characterized by heterogeneous expression and noninternalization of antibody-antigen complexes. Cancer Res 51:2965–72 [Google Scholar]
  12. Trail PA, Willner D, Lasch SJ. 12.  et al. 1993. Cure of xenografted human carcinomas by BR96-doxorubicin immunoconjugates. Science 261:212–15 [Google Scholar]
  13. Petersen BH, DeHerdt SV, Schneck DW. 13.  et al. 1991. The immune response to KS1/4-desacetylvinblastine (LY256787) and KS1/4-desacetylvinblastine hydrazide (LY203728) in single and multiple dose clinical studies. Cancer Res 51:2286–90 [Google Scholar]
  14. Tolcher AW. 14.  2000. BR96-doxorubicin: been there, done that!. J. Clin. Oncol. 18:4000 [Google Scholar]
  15. Thurber GM, Schmidt MM, Wittrup KD. 15.  2008. Antibody tumor penetration: transport opposed by systemic and antigen-mediated clearance. Adv. Drug Deliv. Rev. 60:1421–34 [Google Scholar]
  16. McLarty K, Cornelissen B, Scollard DA. 16.  et al. 2009. Associations between the uptake of 111In-DTPA-trastuzumab, HER2 density and response to trastuzumab (Herceptin) in athymic mice bearing subcutaneous human tumor xenografts. Eur. J. Nucl. Med. Mol. Imag 3681–93 [Google Scholar]
  17. Sedlacek H-H, Seemann G, Hoffmann D. 17.  et al. 1992. Antibodies as carriers of cytotoxicity. Contributions to Oncology H Huber, W Queisser 431–145 Basel, Switz.: Karger [Google Scholar]
  18. Hudziak RM, Lewis GD, Winget M. 18.  et al. 1989. p185HER2 monoclonal antibody has antiproliferative effects in vitro and sensitizes human breast tumor cells to tumor necrosis factor. Mol. Cell Biol. 9:1165–72 [Google Scholar]
  19. Adams GP, Schier R, McCall AM. 19.  et al. 2001. High affinity restricts the localization and tumor penetration of single-chain Fv antibody molecules. Cancer Res 61:4750–55 [Google Scholar]
  20. Doronina SO, Toki BE, Torgov MY. 20.  et al. 2003. Development of potent monoclonal antibody auristatin conjugates for cancer therapy. Nat. Biotechnol. 21:778–84 [Google Scholar]
  21. Widdison WC, Wilhelm SD, Cavanagh EE. 21.  et al. 2006. Semisynthetic maytansine analogues for the targeted treatment of cancer. J. Med. Chem 494392–408 [Google Scholar]
  22. Smith AL, Nicolaou KC. 22.  1996. The enediyne antibiotics. J. Med. Chem 392103–17 [Google Scholar]
  23. Elgersma RC, Coumans RG, Huijbregts T. 23.  et al. 2015. Design, synthesis, and evaluation of linker-duocarmycin payloads: toward selection of HER2-targeting antibody-drug conjugate SYD985. Mol. Pharm. 12:1813–35 [Google Scholar]
  24. Kung Sutherland MS, Walter RB, Jeffrey SC. 24.  et al. 2013. SGN-CD33A: a novel CD33-targeting antibody-drug conjugate using a pyrrolobenzodiazepine dimer is active in models of drug-resistant AML. Blood 122:1455–63 [Google Scholar]
  25. Miller ML, Fishkin NE, Li W. 25.  et al. 2016. A new class of antibody-drug conjugates with potent DNA alkylating activity. Mol. Cancer Ther. 15:1870–78 [Google Scholar]
  26. Senter PD. 26.  2009. Potent antibody drug conjugates for cancer therapy. Curr. Opin. Chem. Biol. 13:235–44 [Google Scholar]
  27. Singh R, Lambert JM, Chari RV. 27.  2014. Antibody-drug conjugates: new frontier in cancer therapeutics. Handbook of Therapeutic Antibodies S Dübel, JM Reichert 341–62 Hoboken, NJ: Wiley, 2nd ed.. [Google Scholar]
  28. Erickson HK, Park PU, Widdison WC. 28.  et al. 2006. Antibody-maytansinoid conjugates are activated in targeted cancer cells by lysosomal degradation and linker-dependent intracellular processing. Cancer Res 66:4426–33 [Google Scholar]
  29. Doronina SO, Mendelsohn BA, Bovee TD. 29.  et al. 2006. Enhanced activity of monomethylauristatin F through monoclonal antibody delivery: effects of linker technology on efficacy and toxicity. Bioconjug. Chem. 17:114–24 [Google Scholar]
  30. Lai KC, Deckert J, Setiady YY. 30.  et al. 2015. Evaluation of targets for maytansinoid ADC therapy using a novel radiochemical assay. Pharm. Res. 32:3593–603 [Google Scholar]
  31. Kovtun YV, Audette CA, Ye Y. 31.  et al. 2006. Antibody-drug conjugates designed to eradicate tumor with homogeneous and heterogeneous expression of the target antigen. Cancer Res 66:3214–21 [Google Scholar]
  32. Polson AG, Calemine-Fenaux J, Chan P. 32.  et al. 2009. Antibody-drug conjugates for the treatment of non-Hodgkin's lymphoma: target and linker-drug selection. Cancer Res 69:2358–64 [Google Scholar]
  33. Widdison WC, Ponte JF, Coccia JA. 33.  et al. 2015. Development of anilino-maytansinoid ADCs that efficiently release cytotoxic metabolites in cancer cells and induce high levels of bystander killing. Bioconjug. Chem. 26:2261–78 [Google Scholar]
  34. Zhao RY, Wilhelm SD, Audette C. 34.  et al. 2011. Synthesis and evaluation of hydrophilic linkers for antibody-maytansinoid conjugates. J. Med. Chem 543606–23 [Google Scholar]
  35. Kovtun YV, Audette CA, Mayo MF. 35.  et al. 2010. Antibody-maytansinoid conjugates designed to bypass multidrug resistance. Cancer Res 70:2528–37 [Google Scholar]
  36. Hong EE, Erickson H, Lutz RJ. 36.  et al. 2015. Design of coltuximab ravtansine, a CD19-targeting antibody-drug conjugate (ADC) for the treatment of B-cell malignancies: structure-activity relationships and preclinical evaluation. Mol. Pharm. 12:1703–16 [Google Scholar]
  37. Sun X, Ponte JF, Yoder NC. 37.  et al. 2017. Effects of drug-antibody ratio on pharmacokinetics, biodistribution, efficacy, and tolerability of antibody-maytansinoid conjugates. Bioconjug. Chem. 28:1371–81 [Google Scholar]
  38. Liu JF, Moore KN, Wang JS. 38.  et al. 2017. Targeting MUC16 with the THIOMABTM-drug conjugate DMUC4064A in patients with platinum-resistant ovarian cancer: a phase I escalation study Am. Assoc. Cancer Res. Annu. Meet. Abstr. CT009
  39. Stein AS, Walter RB, Erba HP. 39.  et al. 2015. A phase I trial of SGN-CD33A as monotherapy in patients with CD33-positive acute myeloid leukemia (AML) Am. Soc. Hematol. Annu. Meet. Abstr324
  40. Sharkey RM, Goldenberg DM. 40.  2008. Use of antibodies and immunoconjugates for the therapy of more accessible cancers. Adv. Drug Delivery Rev. 60:1407–20 [Google Scholar]
  41. Sievers EL, Larson RA, Stadtmauer EA. 41.  et al. 2001. Efficacy and safety of gemtuzumab ozogamicin in patients with CD33-positive acute myeloid leukemia in first relapse. J. Clin. Oncol. 19:3244–54 [Google Scholar]
  42. Bross PF, Beitz J, Chen G. 42.  et al. 2001. Approval summary: gemtuzumab ozogamicin in relapsed acute myeloid leukemia. Clin. Cancer Res. 7:1490–96 [Google Scholar]
  43. Giles FJ, Kantarjian HM, Kornblau SM. 43.  et al. 2001. Mylotarg™ (gemtuzumab ozogamicin) therapy is associated with hepatic venoocclusive disease in patients who have not received stem cell transplantation. Cancer 92:406–13 [Google Scholar]
  44. Petersdorf SH, Kopecky KJ, Slovak M. 44.  et al. 2013. A phase 3 study of gemtuzumab ozogamicin during induction and post-consolidation therapy in younger patients with acute myeloid leukemia. Blood 121:4854–60 [Google Scholar]
  45. Hills RK, Castaigne S, Appelbaum FR. 45.  et al. 2014. Addition of gemtuzumab ozogamicin to induction chemotherapy in adult patients with acute myeloid leukaemia: a meta-analysis of individual patient data from randomized controlled trials. Lancet Oncol 15:986–96 [Google Scholar]
  46. Younes A, Gopal AK, Smith SE. 46.  et al. 2012. Results of a pivotal phase II study of brentuximab vedotin for patients with relapsed or refractory Hodkgin's lymphoma. J. Clin. Oncol. 30:2183–89 [Google Scholar]
  47. Pro B, Advani R, Brice P. 47.  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. 30:2190–96 [Google Scholar]
  48. Younes A, Bartlett NL, Leonard JP. 48.  et al. 2010. Brentuximab vedotin (SGN-35) for relapsed CD30-positive lymphomas. N. Engl. J. Med. 363:1812–21 [Google Scholar]
  49. Moskowitz CH, Nademanee A, Masszi T. 49.  et al. 2015. Brentuximab vedotin as consolidation therapy after autologous stem-cell transplantation in patients with Hodgkin's lymphoma at risk of relapse or progression (AETHERA): a randomized, double-blind, placebo-controlled, phase 3 trial. Lancet 385:1853–62 [Google Scholar]
  50. Prince HM, Kim YH, Horwitz SM. 50.  et al. 2017. Brentuximab vedotin or physician's choice in CD30-positive cutaneous T-cell lymphoma (ALCANZA): an international, open-label, randomized, phase 3, multicenter trial. Lancet 17:31266–67 [Google Scholar]
  51. DiJoseph JF, Armellino DC, Boghaert ER. 51.  et al. 2004. Antibody-targeted chemotherapy with CMC-544: a CD22-targeted immunoconjugate of calicheamicin for the treatment of B-lymphoid malignancies. Blood 103:1807–14 [Google Scholar]
  52. Kantarjian HM, DeAngelo DJ, Stelljes M. 52.  et al. 2016. Inotuzumab ozogamicin versus standard therapy for acute lymphoblastic leukemia. N. Engl. J. Med. 375:740–53 [Google Scholar]
  53. Guffroy M, Falahatpisheh H, Biddle K. 53.  et al. 2017. Liver microvascular injury and thrombocytopenia of antibody-calicheamicin conjugates in cynomolgus monkeys—mechanism and monitoring. Clin. Cancer Res. 23:1760–70 [Google Scholar]
  54. Godwin CD, McDonald GB, Walter RB. 54.  2017. Sinusoidal obstruction syndrome following CD33-targeted therapy in acute myeloid leukemia. Blood 129:2330–32 [Google Scholar]
  55. Fathi AT, Erba HP, Lancet JE. 55.  et al. 2016. Vadastuximab talirine plus hypomethylating agents: a well-tolerated regimen with high remission rate in frontline older patients with acute myeloid leukemia (AML) Am. Soc. Hematol. Annu. Meet. Abstr. 591
  56. Hochhauser D, Meyer T, Spanswick VJ. 56.  et al. 2009. Phase I study of sequence-selective minor groove DNA binding agent SJG-136 in patients with advanced solid tumors. Clin. Cancer Res. 15:2140–47 [Google Scholar]
  57. Verma S, Miles D, Gianni L. 57.  et al. 2012. Trastuzumab emtansine for HER2-positive advanced breast cancer. N. Engl. J. Med. 367:1783–91 [Google Scholar]
  58. Krop IE, Beeram M, Modi S. 58.  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. 28:2698–704 [Google Scholar]
  59. Burris HA III, Rugo HS, Vukelja SJ. 59.  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. 29:398–405 [Google Scholar]
  60. Krop IE, LoRusso P, Miller KD. 60.  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. 30:3234–41 [Google Scholar]
  61. Lambert JM, Morris CQ. 61.  2017. Antibody-drug conjugates (ADCs) for personalized treatment of solid tumors: a review. Adv. Ther. 34:1015–35 [Google Scholar]
  62. Krop IE, Kim S-B, González-Martin A. 62.  et al. 2014. Trastuzumab emtansine versus treatment of physician's choice for pretreated HER2-positive advanced breast cancer (TH3RESA): a randomised, open-lable, phase 3 trial. Lancet Oncol 15:689–99 [Google Scholar]
  63. Carlson RM. 63.  2016. TH3RESA trial: in advanced HER2+ breast cancer overall survival with T-DM1 beats “physician's choice.”. Oncol. Times 38:32–33 [Google Scholar]
  64. Perez EA, Barrios C, Eiermann W. 64.  et al. 2016. Trastuzumab emtansine with or without pertuzumab versus trastuzumab plus taxane for human epidermal growth factor receptor 2–positive, advanced breast cancer: primary results from the phase III MARIANNE study. J. Clin. Oncol. 35:141–48 [Google Scholar]
  65. Hurvitz SA, Dirix L, Kocsis J. 65.  et al. 2013. Phase II randomized study of trastuzumab emtansine versus trastuzumab plus docetaxel in patients with human epidermal growth factor receptor 2–positive metastatic breast cancer. J. Clin. Oncol. 31:1157–63 [Google Scholar]
  66. Miller KD, Diéras V, Harbeck N. 66.  et al. 2014. Phase IIa trial of trastuzumab emtansine with pertuzumab for patients with human epidermal growth factor receptor 2–positive, locally advanced, or metastatic breast cancer. J. Clin. Oncol. 32:1437–44 [Google Scholar]
  67. Lewis Phillips GD, Fields CT, Li G. 67.  et al. 2014. Dual targeting of HER2-positive cancer with trastuzumab emtansine and pertuzumab: critical role for neuregulin blockade in antitumor response to combination therapy. Clin. Cancer Res. 20:456–68 [Google Scholar]
  68. Golfier S, Kopitz C, Kahnert A. 68.  et al. 2014. Anetumab ravtansine: a novel mesothelin-targeting antibody-drug conjugate cures tumors with heterogeneous target expression favored by bystander effect. Mol. Cancer Ther. 13:1537–48 [Google Scholar]
  69. Blumenschein GR, Hassan R, Moore KN. 69.  et al. 2016. Phase I study of anti-mesothelin antibody-drug conjugate anetumab ravtansine (AR). Am. Soc. Clin. Oncol. Meet. Abstr. 2509
  70. Hassan R, Bendell JC, Blumenschein G Jr.. 70.  et al. 2015. Phase I study of anti-mesothelin antibody-drug conjugate anetumab ravtansine (BAY 94-9394) Presentation No. 1574 World Conf. Lung Cancer, 16th. Denver, CO:
  71. Hassan R, Jennens R, van Meerbeeck JP. 71.  et al. 2016. A pivotal randomized phase II study of anetumab ravtansine or vinorelbine in patients with advanced or pleural metastatic mesothelioma after progression on platinum/pemetrexed-based chemotherapy (NCT02610140) Am. Soc. Clin. Oncol. Meet. Abstr. TPS8576
  72. Ab O, Whiteman KR, Bartle LM. 72.  et al. 2015. IMGN853, a folate receptor-α (FRα)-targeting antibody-drug conjugate, exhibits potent targeted antitumor activity against FRα-expressing tumors. Mol. Cancer Ther. 14:1605–13 [Google Scholar]
  73. Moore KN, Borghaei H, O'Malley DM. 73.  et al. 2017. Phase 1 dose-escalation study of mirvetuximab soravtansine (IMGN853), a folate receptor α–targeting antibody-drug conjugate, in patients with solid tumors. Cancer 123:3080–87 [Google Scholar]
  74. Ribrag V, Dupuis J, Tilly H. 74.  et al. 2014. A dose-escalation study of SAR3419, an anti-CD19 antibody maytansinoid conjugate, administered by intravenous infusion once weekly in patients with relapsed/refractory B-cell non-Hodgkin lymphoma. Clin. Cancer Res. 20:213–20 [Google Scholar]
  75. Moskowitz CH, Fanale MA, Shah BD. 75.  et al. 2015. A phase I study of denintuzumab mafadotin (SGN-CD19A) in relapsed/refractory B-lineage non-Hodgkin lymphoma. Am. Soc. Hematol. Annu. Meet. Abstr. 182
  76. Ibrahim NK, Desai N, Legha S. 76.  et al. 2002. Phase 1 and pharmacokinetic study of ABI-007, a Cremophor-free, protein stabilized, nanoparticle formulation of paclitaxel. Clin. Cancer Res. 8:1038–44 [Google Scholar]
  77. Moore KN, Martin LP, O'Malley DM. 77.  et al. 2017. Safety and activity of mirevetuximab soravtansine (IMGN853), a folate receptor alpha–targeting antibody-drug conjugate, in platinum-resistant ovarian cancer, fallopian tube, or primary peritoneal cancer: a phase 1 expansion study. J. Clin. Oncol. 35:1112–18 [Google Scholar]
  78. Moore KN, Matulonis UA, O'Malley DM. 78.  et al. 2017. Mirvetuximab soravtansine (IMGN853), a folate receptor alpha (FRα)–targeting antibody-drug conjugate (ADC), in platinum-resistant epithelial ovarian cancer (EOC) patients (pts): activity and safety analysis in phase I pooled expansion cohorts. Am. Soc. Clin. Oncol. Meet. Abstr. 5547
  79. Gunderson CC, Moore KN. 79.  2016. Mirvetuximab soravtansine: FRα-targeting ADC treatment of epithelial ovarian cancer. Drugs Future 41:539–45 [Google Scholar]
  80. Moore KN, Vergote I, Oaknin A. 80.  et al. 2017. FORWARD I (GOG 3011): a randomized phase 3 study to evaluate the safety and efficacy of mirvetuximab soravtansine (IMGN853) versus chemotherapy in adults with folate receptor alpha (FRα)–positive, platinum-resistant epithelial ovarian cancer (EOC), primary periotoneal cancer, or primary fallopian tube cancer. Am. Soc. Clin. Oncol. Meet. AbstrTPS5607
  81. Saunders LR, Bankovich AJ, Anderson WC. 81.  et al. 2015. A DLL3-targeted antibody-drug conjugate eradicates high-grade pulmonary neuroendocrine tumor-initiating cells in vivo. Sci. Transl. Med. 7:302302ra136 [Google Scholar]
  82. Rudin CM, Pietanza MC, Bauer TM. 82.  et al. 2017. Rovalpituzumab tesirine, a DLL3-targeted antibody-drug conjugate, in recurrent small-cell lung cancer: a first-in-human, first-in-class, open-label, phase 1 study. Lancet Oncol 18:42–51 [Google Scholar]
  83. Simos D, Sajjady G, Sergi M. 83.  et al. 2014. Third-line chemotherapy in small-cell lung cancer: an international analysis. Clin. Lung Cancer 15:110–18 [Google Scholar]
  84. O'Malley DM, Moore KN, Vergote I. 84.  et al. 2017. Safety findings from FORWARD II: a phase 1b study evaluating the folate receptor alpha (FRα)–targeting antibody-drug conjugate (ADC) mirvetuximab soravtansine (IMGN853) in combination with bevacizumab, carboplatin, pegylated liposomal doxorubicin (PLD), or pembrolizumab in patients (pts) with ovarian cancer Am. Soc. Clin. Oncol. Meet. Abstr5553
  85. Müller P, Martin K, Theurich S. 85.  et al. 2014. Microtubule-depolymerizing agents used in antibody-drug conjugates induce antitumor immunity by stimulation of dendritic cells. Cancer Immunol. Res. 2:741–55 [Google Scholar]
  86. Martin K, Müller P, Schreiner J. 86.  et al. 2014. The microtubule-depolymerizing agent ansamitocin P3 programs dendritic cells toward enhanced anti-tumor immunity. Cancer Immunol. Immunother. 63:925–38 [Google Scholar]
  87. Martin K, Schreiner J, Zippelius A. 87.  2015. Modulation of APC function and anti-tumor immunity by anti-cancer drugs. Front. Immunol. 6:501 [Google Scholar]
  88. Müller P, Kreuzaler M, Khan T. 88.  et al. 2015. Trastuzumab emtansine (T-DM1) renders HER2+ breast cancer highly susceptible to CTLA-4/PD-1 blockade. Sci. Transl. Med. 7:315315ra188 [Google Scholar]
  89. Rio-Doria J, Harper J, Rothstein R. 89.  et al. 2017. Antibody-drug conjugates bearing pyrrolobenzodiazepine or tubulysin payloads are immunomodulatory and synergize with multiple immunotherapies. Cancer Res 77:2686–98 [Google Scholar]
  90. Lyon RP, Bovee TD, Doronina SO. 90.  et al. 2015. Reducing hydrophobicity of homogeneous antibody-drug conjugates improves pharmacokinetics and therapeutic index. Nat. Biotechnol. 33:733–35 [Google Scholar]
  91. Dornan D, Bennett F, Chen Y. 91.  et al. 2009. Therapeutic potential of an anti-CD79b antibody-drug conjugate, anti-CD79b-vc-MMAE, for the treatment of non-Hodgkin lymphoma. Blood 114:2721–29 [Google Scholar]
  92. Deckert J, Park PU, Chicklas S. 92.  et al. 2013. A novel anti-CD37 antibody-drug conjugate with multiple anti-tumor mechanisms for the treatment of B-cell malignancies. Blood 122:3500–10 [Google Scholar]
  93. Schönfeld K, Zuber C, Pinkas J. 93.  et al. 2017. Indatuximab ravtansine (BT062) combination treatment in multiple myeloma: pre-clinical studies. J. Hematol. Oncol. 10:13 [Google Scholar]
  94. Bardia A, Mayer IA, Diamond JR. 94.  et al. 2017. Efficacy and safety of any-Trop-2 antibody-drug conjugate sacituzumab govitecan (IMMU-132) in heavily pretreated patients with metastatic triple-negative breast cancer. J. Clin. Oncol. 35:2141–48 [Google Scholar]
  95. Yardley DA, Weaver R, Melisko ME. 95.  et al. 2015. EMERGE: a randomized phase II study of the antibody-drug conjugate glembatumumab vedotin in advanced glycoprotein NMB-expressing breast cancer. J. Clin. Oncol. 33:1609–19 [Google Scholar]
  96. Phillips AC, Boghaert ER, Vaidya KS. 96.  et al. 2016. ABT-414, an antibody-drug conjugate targeting a tumor-selective EGFR epitope. Mol. Cancer Ther. 15:661–69 [Google Scholar]
  97. Donate F, Raitano A, Morrison K. 97.  et al. 2016. AGS16F is a novel antibody drug conjugate directed against ENPP3 for the treatment of renal cell carcinoma. Clin. Cancer Res. 22:1989–99 [Google Scholar]
  98. Gomez-Roca CA, Boni V, Moreno V. 98.  et al. 2016. A phase I study of SAR566658, an anti CA6-antibody drug conjugate (ADC), in patients (Pts) with CA6-positive advanced solid tumors (STs) (NCT01156870). Am. Soc. Clin. Oncol. Meet. Abstr. 2511
  99. DiPippo VA, Olson WC, Nguyen HM. 99.  et al. 2015. Efficacy studies of an antibody-drug conjugate PSMA-ADC in patient-derived prostate cancer xenografts. Prostate 75:303–13 [Google Scholar]
  100. Jones TD, Carter PJ, Plückthun A. 100.  et al. 2016. The INNs and outs of antibody nonproprietary names. MABS 8:1–9 [Google Scholar]
  101. Ponte JF, Ab O, Lanieri L. 101.  et al. 2016. Mirvetuximab soravtansine (IMGN853), a folate receptor alpha–targeting antibody-drug conjugate, potentiates the activity of standard of care therapeutics in ovarian cancer models. Neoplasia 18:775–84 [Google Scholar]
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