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

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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 It was withdrawn from the US market in 2010 following an unsuccessful confirmatory trial.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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Fig. 1 a Chemical structures of the cytotoxic payloads adapted for use in approved and marketed ADCs. b Schematic representations of the structure of ado-trastuzumab emtansine (T-DM1)CC BY-NC · PubMed Central

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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: Life Sciences › Immunology and Microbiology › Immunology › 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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