Antibody–Drug Conjugates (ADCs) for Personalized Treatment of Solid Tumors: A Review

Lambert, John M.; Morris, Charles Q.

doi:10.1007/s12325-017-0519-6

Cited by 304Monoclonal and Polyclonal Antibodies ResearchToxin Mechanisms and ImmunotoxinsNanoparticle-Based Drug Delivery

Antibody–Drug Conjugates (ADCs) for Personalized Treatment of Solid Tumors: A Review

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Lambert, John M., Morris, Charles Q.·2017·Advances in Therapy

DOI 10.1007/s12325-017-0519-6PMC PMC5427099

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Abstract

Attaching a cytotoxic "payload" to an antibody to form an antibody-drug conjugate (ADC) provides a mechanism for selective delivery of the cytotoxic agent to cancer cells via the specific binding of the antibody to cancer-selective cell surface molecules. The first ADC to receive marketing authorization was gemtuzumab ozogamicin, which comprises an anti-CD33 antibody conjugated to a highly potent DNA-targeting antibiotic, calicheamicin, approved in 2000 for treating acute myeloid leukemia. It was withdrawn from the US market in 2010 following an unsuccessful confirmatory trial. The development of two classes of highly potent microtubule-disrupting agents, maytansinoids and auristatins, as payloads for ADCs resulted in approval of brentuximab vedotin in 2011 for treating Hodgkin lymphoma and anaplastic large cell lymphoma, and approval of ado-trastuzumab emtansine in 2013 for treating HER2-positive breast cancer. Their success stimulated much research into the ADC approach, with >60 ADCs currently in clinical evaluation, mostly targeting solid tumors. Five ADCs have advanced into pivotal clinical trials for treating various solid tumors-platinum-resistant ovarian cancer, mesothelioma, triple-negative breast cancer, glioblastoma, and small cell lung cancer. The level of target expression is a key parameter in predicting the likelihood of patient benefit for all these ADCs, as well as for the approved compound, ado-trastuzumab emtansine. The development of a patient selection strategy linked to target expression on the tumor is thus critically important for identifying the population appropriate for receiving treatment.

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ADCs bind to cell surface receptors that are upregulated by mutant RAS.
“They bind to cell surface receptors that are upregulated by mutant RAS and exhibit potent antitumor activity, demonstrating their efficacy in targeting undruggable proteins outside the cell.645–649”
From Recent advances in targeting the “undruggable” proteins: from drug discovery to clinical trials (2023) · cites this paper as [646]
ADCs demonstrate efficacy in targeting undruggable proteins outside the cell.
“They bind to cell surface receptors that are upregulated by mutant RAS and exhibit potent antitumor activity, demonstrating their efficacy in targeting undruggable proteins outside the cell.645–649”
From Recent advances in targeting the “undruggable” proteins: from drug discovery to clinical trials (2023) · cites this paper as [646]
ADCs exhibit potent antitumor activity.
“They bind to cell surface receptors that are upregulated by mutant RAS and exhibit potent antitumor activity, demonstrating their efficacy in targeting undruggable proteins outside the cell.645–649”
From Recent advances in targeting the “undruggable” proteins: from drug discovery to clinical trials (2023) · cites this paper as [646]

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McLarty, K., Cornelissen, B. T., Scollard, D. A., Done, S. J., Chun, K., & Reilly, R. M. (2008) · European Journal of Nuclear Medicine and Molecular Imaging · doi:10.1007/s00259-008-0923-x · Cited by 124 · see citing works
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
Ribrag, V., Dupuis, J., Tilly, H., Morschhauser, F., Lainé, F., Houot, R., Haïoun, C., Copie‐Bergman, C., Varga, A., Lambert, J. M., et al. (2013) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-13-0580 · Cited by 105 · see citing works
Self-citation
A phase 1 study of weekly dosing of trastuzumab emtansine (T‐DM1) in patients with advanced human epidermal growth factor 2–positive breast cancer
Beeram, M., Krop, I. E., Burris, H. A., Girish, S., Yu, W., Lu, M. W., Holden, S. N., & Modi, S. (2012) · Cancer · doi:10.1002/cncr.27622 · Cited by 103 · see citing works
Phase II trial of dolastatin-10 in patients with advanced breast cancer
Perez, E. A., Hillman, D. W., Fishkin, P. A. S., Krook, J. E., Tan, W. W., Kuriakose, P., Alberts, S. R., & Dakhil, S. R. (2005) · Investigational New Drugs · doi:10.1007/s10637-005-6735-y · Cited by 102 · see citing works
Phase I trial of dolastatin-10 (NSC 376128) in patients with advanced solid tumors.
Pitot, H. C., McElroy, E., Reid, J. M., Windebank, A. J., Sloan, J. A., Erlichman, C., Bagniewski, P. G., Walker, D. L., Rubin, J., Goldberg, R. M., et al. (1999) · PubMed · Cited by 101 · see citing works
Anti-NaPi2b antibody–drug conjugate lifastuzumab vedotin (DNIB0600A) compared with pegylated liposomal doxorubicin in patients with platinum-resistant ovarian cancer in a randomized, open-label, phase II study
Banerjee, S. N., Oza, A. M., Birrer, M. J., Hamilton, E. P., Hasan, J., Leary, A. F., Moore, K. N., Maćkowiak-Matejczyk, B., Pikiel, J., Ray-Coquard, I., et al. (2018) · Annals of Oncology · doi:10.1093/annonc/mdy023 · Cited by 101 · see citing works
Phase I/II Study of the Antibody-Drug Conjugate Glembatumumab Vedotin in Patients With Advanced Melanoma
Ott, P. A., Hamid, O., Pavlick, A. C., Kluger, H. M., Kim, K. B., Boasberg, P. D., Simantov, R., Crowley, E. M., Green, J. A., Hawthorne, T. R., et al. (2014) · Journal of Clinical Oncology · doi:10.1200/jco.2013.54.8115 · Cited by 97 · see citing works
A population pharmacokinetic/pharmacodynamic model of thrombocytopenia characterizing the effect of trastuzumab emtansine (T-DM1) on platelet counts in patients with HER2-positive metastatic breast cancer
Bender, B. C., Stark, F. S., Koch, R., Joshi, A., Chu, Y., Rugo, H. S., Krop, I. E., Girish, S., Friberg, L. E., & Gupta, M. (2012) · Cancer Chemotherapy and Pharmacology · doi:10.1007/s00280-012-1934-7 · Cited by 90 · see citing works
Tumor inhibitors. 124. Structural requirements for antileukemic activity among the naturally occurring and semisynthetic maytansinoids
Kupchan, S. M., Sneden, A. T., Branfman, A. R., Howie, G. A., Rebhun, L. I., McIvor, W. E., Wang, R. W., & Schnaitman, T. C. (1978) · Journal of Medicinal Chemistry · doi:10.1021/jm00199a006 · Cited by 88 · see citing works
Phase IIa Trial of Trastuzumab Emtansine With Pertuzumab for Patients With Human Epidermal Growth Factor Receptor 2–Positive, Locally Advanced, or Metastatic Breast Cancer
Miller, K. D., Dieras, V. C., Harbeck, N., André, F., Mahtani, R. L., Gianni, L., Albain, K. S., Crivellari, D., Fang, L., Michelson, G. C., et al. (2014) · Journal of Clinical Oncology · doi:10.1200/jco.2013.52.6590 · Cited by 85 · see citing works
A tribute to Sidney Farber – the father of modern chemotherapy
Miller, D. R. (2006) · British Journal of Haematology · doi:10.1111/j.1365-2141.2006.06119.x · Cited by 82 · see citing works
The microtubule-depolymerizing agent ansamitocin P3 programs dendritic cells toward enhanced anti-tumor immunity
Martin, K., Müller, P., Schreiner, J., Prince, S. S., Lardinois, D., Heinzelmann-Schwarz, V. A., Thommen, D. S., & Zippelius, A. (2014) · Cancer Immunology Immunotherapy · doi:10.1007/s00262-014-1565-4 · Cited by 78 · see citing works
Phase II Study of Dolastatin-10 as First-Line Treatment for Advanced Colorectal Cancer
Saad, E. D., Kraut, E. H., Hoff, P. M., Moore, D. F., JONES, D. M., Pazdur, R., & Abbruzzese, J. L. (2002) · American Journal of Clinical Oncology · doi:10.1097/00000421-200210000-00005 · Cited by 63 · see citing works
Use of antibodies and immunoconjugates for the therapy of more accessible cancers
Sharkey, R. M., & Goldenberg, D. M. (2008) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2008.04.011 · Cited by 62 · see citing works
The INNs and outs of antibody nonproprietary names
Jones, T. D., Carter, P. J., Plückthun, A., Vásquez, M., Holgate, R., Hötzel, I., Popplewell, A. G., Parren, P. W. H. I., Enzelberger, M. M., Rademaker, H. J., et al. (2015) · mAbs · doi:10.1080/19420862.2015.1114320 · Cited by 60 · see citing works
Self-citation
Relationship between HER2 expression and efficacy with first-line trastuzumab emtansine compared with trastuzumab plus docetaxel in TDM4450g: a randomized phase II study of patients with previously untreated HER2-positive metastatic breast cancer
Perez, E. A., Hurvitz, S. A., Amler, L. C., Mundt, K., Ng, V., Guardino, E., & Gianni, L. (2014) · Breast Cancer Research · doi:10.1186/bcr3661 · Cited by 58 · see citing works
A Phase 1 Study of Denintuzumab Mafodotin (SGN-CD19A) in Relapsed/Refactory B-Lineage Non-Hodgkin Lymphoma
Moskowitz, C. H., Fanale, M. A., Shah, B. D., Advani, R. H., Chen, R., Kim, S. Y., Kostić, A., Liu, T., Peng, J. Z., & Forero, A. (2015) · Blood · doi:10.1182/blood.v126.23.182.182 · Cited by 48 · see citing works
Modulation of APC Function and Anti-Tumor Immunity by Anti-Cancer Drugs
Martin, K., Schreiner, J., & Zippelius, A. (2015) · Frontiers in Immunology · doi:10.3389/fimmu.2015.00501 · Cited by 46 · see citing works
A phase 1 study of ABT-806 in subjects with advanced solid tumors
Cleary, J. M., Reardon, D. A., Azad, N. S., Gandhi, L., Shapiro, G. I., Chaves, J. M., Pedersen, M., Ansell, P. J., Ames, W., Xiong, H., et al. (2015) · Investigational New Drugs · doi:10.1007/s10637-015-0234-6 · Cited by 40 · see citing works
A New Triglycyl Peptide Linker for Antibody–Drug Conjugates (ADCs) with Improved Targeted Killing of Cancer Cells
Singh, R., Setiady, Y. Y., Ponte, J. F., Kovtun, Y., Lai, K. C., Hong, E., Fishkin, N. E., Dong, L., Jones, G. E., Coccia, J. A., et al. (2016) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-16-0021 · Cited by 38 · see citing works
Self-citation
A phase I study of SAR566658, an anti CA6-antibody drug conjugate (ADC), in patients (Pts) with CA6-positive advanced solid tumors (STs)(NCT01156870).
Gomez‐Roca, C., Boni, V., Moreno, V., Morris, J. C., Delord, J., Calvo, E., Papadopoulos, K. P., Rixe, O., Cohen, P., Tellier, A., et al. (2016) · Journal of Clinical Oncology · doi:10.1200/jco.2016.34.15_suppl.2511 · Cited by 38 · see citing works
Phase I study of anti-mesothelin antibody drug conjugate anetumab ravtansine (AR).
Blumenschein, G. R., Hassan, R., Moore, K. N., Santin, A. D., Kindler, H. L., Nemunaitis, J. J., Seward, S. M., Rajagopalan, P., Walter, A. O., Sarapa, N., et al. (2016) · Journal of Clinical Oncology · doi:10.1200/jco.2016.34.15_suppl.2509 · Cited by 37 · see citing works
A therapeutic trial of maytansine.
Blum, R. H., Bk, W., Canellos, G. P., Mayer, R. J., Skarin, A. T., Henderson, I. C., Parker, L. M., & Frei, E. (1978) · PubMed · Cited by 32 · see citing works
Statistics of the Distribution of the Abundance of Molecules with Various Drug Loads in Maytansinoid Antibody–Drug Conjugates
Goldmacher, V. S., Amphlett, G. W., Wang, L., & Lazar, A. C. (2015) · Molecular Pharmaceutics · doi:10.1021/mp5007536 · Cited by 29 · see citing works
Frequent dosing and GPNMB expression with CDX-011 (CR011-vcMMAE), an antibody-drug conjugate (ADC), in patients with advanced melanoma.
Hamid, O., Sznol, M., Pavlick, A. C., Kluger, H. M., Kim, K. B., Boasberg, P. D., Simantov, R., Davis, T. A., Crowley, E. M., & Hwu, P. (2010) · Journal of Clinical Oncology · doi:10.1200/jco.2010.28.15_suppl.8525 · Cited by 28 · see citing works
Safety and efficacy of single-agent rovalpituzumab tesirine (SC16LD6.5), a delta-like protein 3 (DLL3)-targeted antibody-drug conjugate (ADC) in recurrent or refractory small cell lung cancer (SCLC).
Rudin, C. M., Pietanza, M. C., Bauer, T. M., Spigel, D. R., Ready, N., Morgensztern, D., Glisson, B. S., Byers, L. A., Johnson, M. L., Burris, H. A., et al. (2016) · Journal of Clinical Oncology · doi:10.1200/jco.2016.34.18_suppl.lba8505 · Cited by 24 · see citing works
Phase I study of ABT-414 mono- or combination therapy with temozolomide (TMZ) in recurrent glioblastoma (GBM).
Gan, H. K., Papadopoulos, K. P., Fichtel, L., Lassman, A. B., Merrell, R. T., van den Bent, M. J., Kumthekar, P., Scott, A. M., Pedersen, M., Gomez, E. J., et al. (2015) · Journal of Clinical Oncology · doi:10.1200/jco.2015.33.15_suppl.2016 · Cited by 21 · see citing works
A pivotal randomized phase II study of anetumab ravtansine or vinorelbine in patients with advanced or metastatic pleural mesothelioma after progression on platinum/pemetrexed-based chemotherapy (NCT02610140).
Hassan, R., Jennens, R. R., van Meerbeeck, J. P., Nemunaitis, J. J., Blumenschein, G. R., Fennell, D. A., Kindler, H. L., Novello, S., Elbi, C., Walter, A. O., et al. (2016) · Journal of Clinical Oncology · doi:10.1200/jco.2016.34.15_suppl.tps8576 · Cited by 20 · see citing works
Phase 1 study of IMGN853, a folate receptor alpha (FRα)-targeting antibody-drug conjugate (ADC) in patients (Pts) with epithelial ovarian cancer (EOC) and other FRA-positive solid tumors.
Borghaei, H., O’Malley, D. M., Seward, S. M., Bauer, T. M., Perez, R. P., Oza, A. M., Jeong, W., Michenzie, M. F., Kirby, M. W., Chandorkar, G., et al. (2015) · Journal of Clinical Oncology · doi:10.1200/jco.2015.33.15_suppl.5558 · Cited by 16 · see citing works
Safety and efficacy of single-agent rovalpituzumab tesirine (SC16LD6.5), a delta-like protein 3 (DLL3)-targeted antibody-drug conjugate (ADC) in recurrent or refractory small cell lung cancer (SCLC).
Rudin, C. M., Pietanza, M. C., Bauer, T. M., Spigel, D. R., Ready, N., Morgensztern, D., Glisson, B. S., Byers, L. A., Johnson, M. L., Burris, H. A., et al. (2016) · Journal of Clinical Oncology · doi:10.1200/jco.2016.34.15_suppl.lba8505 · Cited by 14 · see citing works
Typical Antibody–Drug Conjugates
Lambert, J. M. (2016) · doi:10.1002/9781119060727.ch1 · Cited by 12 · see citing works
Self-citation
Mirvetuximab soravtansine. FRalpha-targeting ADC, Treatment of epithelial ovarian cancer
Gunderson, C. C., & Moore, K. (2016) · Drugs of the Future · doi:10.1358/dof.2016.041.09.2544475 · Cited by 10 · see citing works
METRIC: A randomized international study of the antibody-drug conjugate glembatumumab vedotin (GV or CDX-011) in patients (pts) with metastatic gpNMB-overexpressing triple-negative breast cancer (TNBC).
Yardley, D. A., Melisko, M., Forero, A., Daniel, B. R., Montero, A. J., Guthrie, T. H., Canfield, V. A., Oakman, C. A., Chew, H. K., Ferrario, C., et al. (2015) · Journal of Clinical Oncology · doi:10.1200/jco.2015.33.15_suppl.tps1110 · Cited by 9 · see citing works
Efficacy of a novel antibody-drug conjugate (ADC), ABT-414, as monotherapy in epidermal growth factor receptor (EGFR) amplified, recurrent glioblastoma (GBM).
van den Bent, M. J., Gan, H. K., Lassman, A. B., Kumthekar, P., Merrell, R. T., Butowski, N. A., Lwin, Z., Mikkelsen, T., Nabors, B., Papadopoulos, K. P., et al. (2016) · Journal of Clinical Oncology · doi:10.1200/jco.2016.34.15_suppl.2542 · Cited by 9 · see citing works
mTOR inhibition in T-cell lymphoma: a path(way) forward
Moskowitz, A. J., & Horwitz, S. M. (2015) · Blood · doi:10.1182/blood-2015-05-644724 · Cited by 8 · see citing works
Antibody‐Drug Conjugates: New Frontier in Cancer Therapeutics
Singh, R., Lambert, J. M., & Chari, R. V. J. (2014) · doi:10.1002/9783527682423.ch13 · Cited by 7 · see citing works
Self-citation
FORWARD II: A phase Ib study to evaluate the safety, tolerability and pharmacokinetics of mirvetuximab soravtansine (IMGN853) in combination with bevacizumab, carboplatin or pegylated liposomal doxorubicin in adults with folate receptor alpha (FRα)-positive advanced epithelial ovarian cancer (EOC), primary peritoneal, fallopian tube, or endometrial cancer.
O’Malley, D. M., Martin, L. P., Moore, K. N., Nepert, D. L., Ruiz-Soto, R., & Vergote, I. B. (2016) · Journal of Clinical Oncology · doi:10.1200/jco.2016.34.15_suppl.tps5611 · Cited by 6 · see citing works
A randomized, open-label, phase II study of anti-NaPi2b antibody-drug conjugate (ADC) lifastuzumab (Lifa) vedotin (DNIB0600A) compared to pegylated liposomal doxorubicin (PLD) in patients (pts) with platinum-resistant ovarian cancer (PROC).
Banerjee, S. N., Oza, A. M., Birrer, M. J., Hamilton, E. P., Hasan, J., Leary, A. F., Moore, K. N., Maćkowiak-Matejczyk, B., Pikiel, J., Ray-Coquard, I. L., et al. (2016) · Journal of Clinical Oncology · doi:10.1200/jco.2016.34.15_suppl.5569 · Cited by 5 · see citing works
Abstract C47: Association of folate receptor alpha (FRα) expression level and clinical activity of IMGN853 (mirvetuximab soravtansine), a FRα-targeting antibody-drug conjugate (ADC), in FRα -expressing platinum-resistant epithelial ovarian cancer (EOC) patients (pts)
Martin, L. P., Moore, K. N., O’Malley, D. M., Seward, S., Bauer, T. M., Perez, R., Jeong, W., Zhou, Y., Ponte, J., Kirby, M. W., et al. (2015) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.targ-15-c47 · Cited by 3 · see citing works
Abstract CT083: A pivotal randomized phase II study of anetumab ravtansine or vinorelbine in patients with advanced or metastatic pleural mesothelioma after progression on platinum/pemetrexed-based chemotherapy (NCT02610140)
Hassan, R., Nemunaitis, J. J., van Meerbeeck, J. P., Jennens, R. R., Blumenschein, G. R., Fennell, D. A., Kindler, H. L., Novello, S., Elbi, C., Walter, A. O., et al. (2016) · Cancer Research · doi:10.1158/1538-7445.am2016-ct083 · Cited by 2 · see citing works
Simoneʼs OncOpinion
Simone, J. V. (2016) · Oncology Times · doi:10.1097/01.cot.0000480924.48580.fc · Cited by 1 · see citing works
TH3RESA Trial
Carlson, R. H. (2016) · Oncology Times · doi:10.1097/01.cot.0000480876.05852.d5 · Cited by 1 · see citing works

Flagged first, then by citations

Sorted by citations

Bioorthogonal chemistry
Scinto, S. L., Bilodeau, D. A., Hincapie, R., Lee, W., Nguyen, S. S., Xu, M., Ende, C. W. A., Finn, M. G., Lang, K., Lin, Q., et al. (2021) · Nature Reviews Methods Primers · doi:10.1038/s43586-021-00028-z · Cited by 620 · see citing works
Antibody drug conjugates and bystander killing: is antigen-dependent internalisation required?
Staudacher, A. H., & Brown, M. P. (2017) · British Journal of Cancer · doi:10.1038/bjc.2017.367 · Cited by 546 · see citing works
Antibody-Drug Conjugate-Based Therapeutics: State of the Science
Birrer, M. J., Moore, K. N., Betella, I., & Bates, R. C. (2019) · JNCI Journal of the National Cancer Institute · doi:10.1093/jnci/djz035 · Cited by 442 · see citing works
Recent advances in targeting the “undruggable” proteins: from drug discovery to clinical trials
Xie, X., Yu, T., Li, X., Zhang, N., Foster, L. J., Peng, C., Huang, W., & He, G. (2023) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-023-01589-z · Cited by 396 · see citing works
Antibody–Drug Conjugates: The Last Decade
Joubert, N., Beck, A., Dumontet, C., & Denevault‐Sabourin, C. (2020) · Pharmaceuticals · doi:10.3390/ph13090245 · Cited by 371 · see citing works
Antibody–Drug Conjugates for Cancer Treatment
Lambert, J. M., & Berkenblit, A. (2018) · Annual Review of Medicine · doi:10.1146/annurev-med-061516-121357 · Cited by 314 · see citing works
Self-citation
Potential mechanisms of target-independent uptake and toxicity of antibody-drug conjugates
Mahalingaiah, P. K., Ciurlionis, R., Durbin, K. R., Yeager, R. L., Philip, B. K., Bawa, B., Mantena, S. R., Enright, B. P., Liguori, M. J., & Van Vleet, T. R. (2019) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2019.04.008 · Cited by 286 · see citing works
Causes, consequences, and therapy of tumors acidosis
Pillai, S., Damaghi, M., Marunaka, Y., Spugnini, E. P., Fais, S., & Gillies, R. J. (2019) · Cancer and Metastasis Reviews · doi:10.1007/s10555-019-09792-7 · Cited by 282 · see citing works
Chemically triggered drug release from an antibody-drug conjugate leads to potent antitumour activity in mice
Rossin, R., Versteegen, R. M., Wu, J., Khasanov, A. B., Wessels, H. J. C. T., Steenbergen, E. J., ten Hoeve, W., Janssen, H. M., van Onzen, A. H. A. M., Hudson, P. J., et al. (2018) · Nature Communications · doi:10.1038/s41467-018-03880-y · Cited by 280 · see citing works
Antibody–drug conjugates (ADCs) for cancer therapy: Strategies, challenges, and successes
Abdollahpour‐Alitappeh, M., Lotfinia, M., Gharibi, T., Mardaneh, J., Farhadihosseinabadi, B., Larki, P., Faghfourian, B., Sepehr, K. S., Abbaszadeh‐Goudarzi, K., Abbaszadeh‐Goudarzi, G., et al. (2018) · Journal of Cellular Physiology · doi:10.1002/jcp.27419 · Cited by 252 · see citing works
LRRC15 Is a Novel Mesenchymal Protein and Stromal Target for Antibody–Drug Conjugates
Purcell, J. W., Tanlimco, S. G., Hickson, J. A., Fox, M., Sho, M., Durkin, L. M., Uziel, T., Powers, R., Foster, K., McGonigal, T. P., et al. (2018) · Cancer Research · doi:10.1158/0008-5472.can-18-0327 · Cited by 207 · see citing works
Mechanisms of Therapeutic Antitumor Monoclonal Antibodies
Tsao, L.-C., Force, J. M., & Hartman, Z. C. (2021) · Cancer Research · doi:10.1158/0008-5472.can-21-1109 · Cited by 205 · see citing works
A comprehensive overview on antibody-drug conjugates: from the conceptualization to cancer therapy
Riccardi, F., Bo, M. D., Macor, P., & Toffoli, G. (2023) · Frontiers in Pharmacology · doi:10.3389/fphar.2023.1274088 · Cited by 203 · see citing works
EGFR targeting for cancer therapy: Pharmacology and immunoconjugates with drugs and nanoparticles
Santos, E. D. S., Nogueira, K. A. B., Crisóstomo, L. C. C. F., Martins, J. R. P., Reis, A. V. F., Neto, J. D. B. V., da Silva, I. J., Pessoa, C., Petrilli, R., & Eloy, J. O. (2020) · International Journal of Pharmaceutics · doi:10.1016/j.ijpharm.2020.120082 · Cited by 186 · see citing works
Chemotherapeutic agents for the treatment of metastatic breast cancer: An update
Abotaleb, M., Kubatka, P., Čaprnda, M., Varghese, E., Zolakova, B., Žúbor, P., Opatřilová, R., Kružliak, P., Štefanička, P., & Büsselberg, D. (2018) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2018.02.108 · Cited by 187 · see citing works
Mitochondrial-Targeting Anticancer Agent Conjugates and Nanocarrier Systems for Cancer Treatment
Battogtokh, G., Cho, Y., Lee, J. Y., Lee, H. S., & Kang, H. C. (2018) · Frontiers in Pharmacology · doi:10.3389/fphar.2018.00922 · Cited by 177 · see citing works
Antibody therapeutics and immunoregulation in cancer and autoimmune disease
Yasunaga, M. (2019) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2019.06.001 · Cited by 164 · see citing works
Advances and Limitations of Antibody Drug Conjugates for Cancer
Mckertish, C. M., & Kayser, V. (2021) · Biomedicines · doi:10.3390/biomedicines9080872 · Cited by 165 · see citing works
Antibody drug conjugates for treatment of breast cancer: Novel targets and diverse approaches in ADC design
Trail, P. A., Dubowchik, G. M., & Lowinger, T. B. (2017) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2017.07.013 · Cited by 136 · see citing works
Challenges and new frontiers in analytical characterization of antibody-drug conjugates
Wagh, A. V., Song, H., Zeng, M., Tao, L., & Das, T. K. (2018) · mAbs · doi:10.1080/19420862.2017.1412025 · Cited by 136 · see citing works
Nanotechnology-based combination therapy for overcoming multidrug-resistant cancer
Zhang, M., Liu, E., Cui, Y., & Huang, Y. (2017) · Cancer Biology and Medicine · doi:10.20892/j.issn.2095-3941.2017.0054 · Cited by 134 · see citing works
Impact of Endocytosis Mechanisms for the Receptors Targeted by the Currently Approved Antibody-Drug Conjugates (ADCs)—A Necessity for Future ADC Research and Development
Hammood, M., Craig, A. W., & Leyton, J. V. (2021) · Pharmaceuticals · doi:10.3390/ph14070674 · Cited by 132 · see citing works
Current status and contemporary approaches to the discovery of antitumor agents from higher plants
Agarwal, G., Carcache, P. J. B., Addo, E. M., & Kinghorn, A. D. (2019) · Biotechnology Advances · doi:10.1016/j.biotechadv.2019.01.004 · Cited by 114 · see citing works
MMAE Delivery Using the Bicycle Toxin Conjugate BT5528
Bennett, G. S., Brown, A. N., Mudd, G., Huxley, P., Rietschoten, K. V., Pavan, S., Chen, L., Watcham, S. M., Lahdenranta, J., & Keen, N. (2020) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-19-1092 · Cited by 105 · see citing works
A Review of Mirvetuximab Soravtansine in the Treatment of Platinum-Resistant Ovarian Cancer
Moore, K. N., Martin, L. P., O’Malley, D. M., Matulonis, U. A., Konner, J. A., Vergote, I. B., Ponte, J. F., & Birrer, M. J. (2017) · Future Oncology · doi:10.2217/fon-2017-0379 · Cited by 101 · see citing works
Drug conjugate-based anticancer therapy - Current status and perspectives
Yang, Y., Wang, S., Ma, P., Jiang, Y., Cheng, K., Yu, Y., Jiang, N., Miao, H., Tang, Q., Liu, F., et al. (2022) · Cancer Letters · doi:10.1016/j.canlet.2022.215969 · Cited by 101 · see citing works
Present and future of cancer nano-immunotherapy: opportunities, obstacles and challenges
Wang, M., Yu, F., & Zhang, Y. (2025) · Molecular Cancer · doi:10.1186/s12943-024-02214-5 · Cited by 105 · see citing works
Current Advancements in Addressing Key Challenges of Therapeutic Antibody Design, Manufacture, and Formulation
Sifniotis, V., Cruz, E., Eroglu, B., & Kayser, V. (2019) · Antibodies · doi:10.3390/antib8020036 · Cited by 99 · see citing works
Small-Format Drug Conjugates: A Viable Alternative to ADCs for Solid Tumours?
Deonarain, M. P., Yahioglu, G., Stamati, I., Pomowski, A., Clarke, J., Edwards, B. M., Diez-Posada, S., & Stewart, A. (2018) · Antibodies · doi:10.3390/antib7020016 · Cited by 92 · see citing works
Photosensitizer Antibody–Drug Conjugates: Past, Present, and Future
Sandland, J., & Boyle, R. W. (2019) · Bioconjugate Chemistry · doi:10.1021/acs.bioconjchem.9b00055 · Cited by 92 · see citing works
Current Therapies for Human Epidermal Growth Factor Receptor 2-Positive Metastatic Breast Cancer Patients
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First-in-Human Phase I Study of ABBV-085, an Antibody–Drug Conjugate Targeting LRRC15, in Sarcomas and Other Advanced Solid Tumors
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Self-citation

Authors: Lambert, J. M., & Morris, C. Q.
Affiliations: ImmunoGen (United States) (US)
Corresponding author: Lambert, John M.
ORCID: Lambert, John M.
Morris, Charles Q.
Venue: Advances in Therapy
Publisher: Springer Science and Business Media LLC
Published: 2017-03-30
Volume: 34
Issue: 5
Pages: 1015-1035
ISSN: 0741-238X (ISSN-L)
1865-8652
DOI: 10.1007/s12325-017-0519-6
PMC: PMC5427099
OpenAlex: W2603088210
Cited by: 304
References: 102
Citations by year: 2026: 30 · 2025: 21 · 2024: 18 · 2023: 24 · 2022: 16 · 2021: 49 · 2020: 48 · 2019: 45 · 2018: 45 · 2017: 7
FWCI: 5.99
Type: journal article
Language: en
Open access: hybrid
doi.org
Licence: cc-by-nc
creativecommons.org/licenses/by/4.0 (tdm)
Locations: Advances in Therapy (publishedVersion, cc-by-nc)
Europe PMC (PubMed Central) (publishedVersion, cc-by-nc)
PubMed Central (publishedVersion, cc-by-nc)
PubMed (publishedVersion)
Topics: Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Monoclonal and Polyclonal Antibodies Research
Life Sciences › Immunology and Microbiology › Immunology › Toxin Mechanisms and Immunotoxins
Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
Keywords: antibody-drug conjugates, solid tumors, precision oncology, targeted drug delivery, maytansinoids, auristatin, calicheamicin, gemtuzumab ozogamicin, brentuximab vedotin, trastuzumab emtansine, target expression, patient selection, platinum-resistant ovarian cancer, mesothelioma, triple-negative breast cancer, glioblastoma, small cell lung cancer, cytotoxic payloads
MeSH terms: Trastuzumab, Gemtuzumab, Ado-Trastuzumab Emtansine, Aminoglycosides, Antineoplastic Agents, Humans, Maytansine, Neoplasms, Oligopeptides, Immunoconjugates, Antibodies, Monoclonal, Humanized, Aminobenzoates, Sialic Acid Binding Ig-like Lectin 3

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Antibody–Drug Conjugates (ADCs) for Personalized Treatment of Solid Tumors: A Review

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