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Home / Equine Research Bank / J Pharmacol Toxicol Methods / Antibody drug conjugates – Trojan horses in the war on...
Journal of pharmacological and toxicological methods2011; 64(3); 207-212; doi: 10.1016/j.vascn.2011.07.005

Antibody drug conjugates – Trojan horses in the war on cancer.

Abstract: Antibody drug conjugates (ADCs) consist of an antibody attached to a cytotoxic drug by means of a linker. ADCs provide a way to couple the specificity of a monoclonal antibody (mAb) to the cytotoxicity of a small-molecule drug and, therefore, are promising new therapies for cancer. ADCs are prodrugs that are inactive in circulation but exert their cytotoxicity upon binding to the target cancer cell. Earlier unsuccessful attempts to generate ADCs with therapeutic value have emphasized the important role each component plays in determining the efficacy and safety of the final ADC. Scientific advances in engineering antibodies for maximum efficacy as anticancer agents, identification of highly cytotoxic molecules, and generation of linkers with increased stability in circulation have all contributed to the development of the many ADCs that are currently in clinical trials. This review discusses parameters that guide the selection of the components of an ADC to increase its therapeutic window, provides a brief look at ADCs currently in clinical trials, and discusses future challenges in this field.
Copyright © 2011. Published by Elsevier Inc.
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Publication Date: 2011-08-06 PubMed ID: 21843648DOI: 10.1016/j.vascn.2011.07.005Google Scholar: Lookup
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Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

This research discusses antibody drug conjugates (ADCs), a new type of treatment for cancer that combines an antibody with a cytotoxic drug. This combination proves to be a promising therapy as it can target only the cancerous cells without affecting the healthy ones. The article also discusses the challenges faced during earlier development of ADC’s and how scientific advancements have improved their overall efficacy and safety.

Understanding Antibody Drug Conjugates (ADCs)

  • ADCs are composed of an antibody linked to a cytotoxic drug, creating a targeted approach to cancer treatment. They are essentially prodrugs, which remain inactive until they bind to their target cancer cell, resulting in decreased side effects and increased effectiveness.
  • The success of an ADC therapy largely hinges on the selection and combination of its components – the monoclonal antibody (mAb), the cytotoxic agent, and the linker that connects them.

Improvement and Advancements in ADC Development

  • Earlier attempts at creating ADCs often failed because the complex role that each component plays was not entirely understood, leading to inefficiencies and safety issues.
  • New developments in biomedical engineering have led to enhanced efficacy of antibodies as anticancer agents, as scientists have learned how to more efficiently couple the monoclonal antibody to the cytotoxic drug.
  • Advancements in chemistry have also played a significant role with the introduction of new, more potent cytotoxic agents and linkers with greater stability, reducing the risk of premature drug release into circulation.

ADCs in Current Clinical Trials

  • The paper includes a brief discussion of different ADCs presently under clinical experimentation. By analyzing the findings of these trials, scientists are further honing the design and delivery of ADCs for maximum therapeutic benefit.

Future Challenges in ADC Research

  • The article concludes by discussing the future challenges in the field, which include understanding and overcoming resistance to ADC treatment, further refining the selectivity and potency of ADCs, and developing new improved linker technology.

Cite This Article

APA
Iyer U, Kadambi VJ. (2011). Antibody drug conjugates – Trojan horses in the war on cancer. J Pharmacol Toxicol Methods, 64(3), 207-212. https://doi.org/10.1016/j.vascn.2011.07.005

Publication

Journal of pharmacological and toxicological methods
ISSN: 1873-488X
NlmUniqueID: 9206091
Country: United States
Language: English
Volume: 64
Issue: 3
Pages: 207-212

Researcher Affiliations

Iyer, U
  • Non-Clinical Development Sciences, Millennium Pharmaceuticals, Inc, Cambridge, MA 02139, USA.
Kadambi, V J

    MeSH Terms

    • Animals
    • Antibodies, Monoclonal / immunology
    • Antibodies, Monoclonal / therapeutic use
    • Antineoplastic Agents / immunology
    • Antineoplastic Agents / therapeutic use
    • Clinical Trials as Topic
    • Humans
    • Immunotoxins / immunology
    • Immunotoxins / therapeutic use
    • Neoplasms / drug therapy
    • Neoplasms / immunology

    Citations

    This article has been cited 32 times.
    1. Thakral D, Gupta R, Khan A. Leukemic stem cell signatures in Acute myeloid leukemia- targeting the Guardians with novel approaches. Stem Cell Rev Rep 2022 Jun;18(5):1756-1773.
      doi: 10.1007/s12015-022-10349-5pubmed: 35412219google scholar: lookup
    2. Sheyi R, de la Torre BG, Albericio F. Linkers: An Assurance for Controlled Delivery of Antibody-Drug Conjugate. Pharmaceutics 2022 Feb 11;14(2).
      doi: 10.3390/pharmaceutics14020396pubmed: 35214128google scholar: lookup
    3. Ye Z, Zhang Y, Liu Y, Liu Y, Tu J, Shen Y. EGFR Targeted Cetuximab-Valine-Citrulline (vc)-Doxorubicin Immunoconjugates- Loaded Bovine Serum Albumin (BSA) Nanoparticles for Colorectal Tumor Therapy. Int J Nanomedicine 2021;16:2443-2459.
      doi: 10.2147/IJN.S289228pubmed: 33814909google scholar: lookup
    4. Wang H, Mooney DJ. Metabolic glycan labelling for cancer-targeted therapy. Nat Chem 2020 Dec;12(12):1102-1114.
      doi: 10.1038/s41557-020-00587-wpubmed: 33219365google scholar: lookup
    5. Wang E, Sorolla MA, Krishnan PDG, Sorolla A. From Seabed to Bedside: A Review on Promising Marine Anticancer Compounds. Biomolecules 2020 Feb 6;10(2).
      doi: 10.3390/biom10020248pubmed: 32041255google scholar: lookup
    6. Harel ET, Drake PM, Barfield RM, Lui I, Farr-Jones S, Van't Veer L, Gartner ZJ, Green EM, Lourenço AL, Cheng Y, Hann BC, Rabuka D, Craik CS. Antibody-Drug Conjugates Targeting the Urokinase Receptor (uPAR) as a Possible Treatment of Aggressive Breast Cancer. Antibodies (Basel) 2019 Nov 5;8(4).
      doi: 10.3390/antib8040054pubmed: 31694242google scholar: lookup
    7. Gull I, Aslam MS, Tipu I, Mushtaq R, Ali TZ, Athar MA. Development of latent Interferon alpha 2b as a safe therapeutic for treatment of Hepatitis C virus infection. Sci Rep 2019 Jul 26;9(1):10867.
      doi: 10.1038/s41598-019-47074-ypubmed: 31350425google scholar: lookup
    8. Agarwal G, Carcache PJB, Addo EM, Kinghorn AD. Current status and contemporary approaches to the discovery of antitumor agents from higher plants. Biotechnol Adv 2020 Jan-Feb;38:107337.
      doi: 10.1016/j.biotechadv.2019.01.004pubmed: 30633954google scholar: lookup
    9. Macdonald J, Henri J, Roy K, Hays E, Bauer M, Veedu RN, Pouliot N, Shigdar S. EpCAM Immunotherapy versus Specific Targeted Delivery of Drugs. Cancers (Basel) 2018 Jan 12;10(1).
      doi: 10.3390/cancers10010019pubmed: 29329202google scholar: lookup
    10. Ankenbruck N, Courtney T, Naro Y, Deiters A. Optochemical Control of Biological Processes in Cells and Animals. Angew Chem Int Ed Engl 2018 Mar 5;57(11):2768-2798.
      doi: 10.1002/anie.201700171pubmed: 28521066google scholar: lookup
    11. Howard D, Garcia-Parra J, Healey GD, Amakiri C, Margarit L, Francis LW, Gonzalez D, Conlan RS. Antibody-drug conjugates and other nanomedicines: the frontier of gynaecological cancer treatment. Interface Focus 2016 Dec 6;6(6):20160054.
      doi: 10.1098/rsfs.2016.0054pubmed: 27920893google scholar: lookup
    12. Malve H. Exploring the ocean for new drug developments: Marine pharmacology. J Pharm Bioallied Sci 2016 Apr-Jun;8(2):83-91.
      doi: 10.4103/0975-7406.171700pubmed: 27134458google scholar: lookup
    13. Lu J, Jiang F, Lu A, Zhang G. Linkers Having a Crucial Role in Antibody-Drug Conjugates. Int J Mol Sci 2016 Apr 14;17(4):561.
      doi: 10.3390/ijms17040561pubmed: 27089329google scholar: lookup
    14. Mao Y, Wang X, Zheng F, Wang C, Tang Q, Tang X, Xu N, Zhang H, Zhang D, Xiong L, Liang J, Zhu J. The tumor-inhibitory effectiveness of a novel anti-Trop2 Fab conjugate in pancreatic cancer. Oncotarget 2016 Apr 26;7(17):24810-23.
      doi: 10.18632/oncotarget.8529pubmed: 27050150google scholar: lookup
    15. Naddafi F, Davami F. Anti-CD19 Monoclonal Antibodies: a New Approach to Lymphoma Therapy. Int J Mol Cell Med 2015 Summer;4(3):143-51.
      pubmed: 26629482
    16. Peters C, Brown S. Antibody-drug conjugates as novel anti-cancer chemotherapeutics. Biosci Rep 2015 Jun 12;35(4).
      doi: 10.1042/BSR20150089pubmed: 26182432google scholar: lookup
    17. Xu S. Internalization, Trafficking, Intracellular Processing and Actions of Antibody-Drug Conjugates. Pharm Res 2015 Nov;32(11):3577-83.
      doi: 10.1007/s11095-015-1729-8pubmed: 26108878google scholar: lookup
    18. Rycroft D, Sosabowski J, Coulstock E, Davies M, Morrey J, Friel S, Kelly F, Hamatake R, Ovečka M, Prince R, Goodall L, Sepp A, Walker A. Pharmacokinetic characteristics, pharmacodynamic effect and in vivo antiviral efficacy of liver-targeted interferon alpha. PLoS One 2015;10(2):e0117847.
      doi: 10.1371/journal.pone.0117847pubmed: 25689509google scholar: lookup
    19. Sun D, Sun M, Zhu W, Wang Z, Li Y, Ma J. The anti-cancer potency and mechanism of a novel tumor-activated fused toxin, DLM. Toxins (Basel) 2015 Feb 4;7(2):423-38.
      doi: 10.3390/toxins7020423pubmed: 25658509google scholar: lookup
    20. Filntisi A, Vlachakis D, Matsopoulos GK, Kossida S. Computational Construction of Antibody-Drug Conjugates Using Surface Lysines as the Antibody Conjugation Site and a Non-cleavable Linker. Cancer Inform 2014;13:179-86.
      doi: 10.4137/CIN.S19222pubmed: 25506200google scholar: lookup
    21. Gurnev PA, Nestorovich EM. Channel-forming bacterial toxins in biosensing and macromolecule delivery. Toxins (Basel) 2014 Aug 21;6(8):2483-540.
      doi: 10.3390/toxins6082483pubmed: 25153255google scholar: lookup
    22. Zinzi L, Contino M, Cantore M, Capparelli E, Leopoldo M, Colabufo NA. ABC transporters in CSCs membranes as a novel target for treating tumor relapse. Front Pharmacol 2014;5:163.
      doi: 10.3389/fphar.2014.00163pubmed: 25071581google scholar: lookup
    23. Li X, Fang T, Boons GJ. Preparation of well-defined antibody-drug conjugates through glycan remodeling and strain-promoted azide-alkyne cycloadditions. Angew Chem Int Ed Engl 2014 Jul 7;53(28):7179-82.
      doi: 10.1002/anie.201402606pubmed: 24862406google scholar: lookup
    24. Deo VK, Yui M, Alam J, Yamazaki M, Kato T, Park EY. A model for targeting colon carcinoma cells using single-chain variable fragments anchored on virus-like particles via glycosyl phosphatidylinositol anchor. Pharm Res 2014 Aug;31(8):2166-77.
      doi: 10.1007/s11095-014-1316-4pubmed: 24570130google scholar: lookup
    25. Newman DJ, Cragg GM. Marine-sourced anti-cancer and cancer pain control agents in clinical and late preclinical development. Mar Drugs 2014 Jan 14;12(1):255-78.
      doi: 10.3390/md12010255pubmed: 24424355google scholar: lookup
    26. Siontorou CG. Nanobodies as novel agents for disease diagnosis and therapy. Int J Nanomedicine 2013;8:4215-27.
      doi: 10.2147/IJN.S39428pubmed: 24204148google scholar: lookup
    27. Rath T, Baker K, Dumont JA, Peters RT, Jiang H, Qiao SW, Lencer WI, Pierce GF, Blumberg RS. Fc-fusion proteins and FcRn: structural insights for longer-lasting and more effective therapeutics. Crit Rev Biotechnol 2015 Jun;35(2):235-54.
      doi: 10.3109/07388551.2013.834293pubmed: 24156398google scholar: lookup
    28. Vlachakis D, Kossida S. Antibody Drug Conjugate bioinformatics: drug delivery through the letterbox. Comput Math Methods Med 2013;2013:282398.
      doi: 10.1155/2013/282398pubmed: 23853668google scholar: lookup
    29. Chen X, Ding G, Gao Q, Sun J, Zhang Q, Du L, Qiu Z, Wang C, Zheng F, Sun B, Ni J, Feng Z, Zhu J. A human anti-c-Met Fab fragment conjugated with doxorubicin as targeted chemotherapy for hepatocellular carcinoma. PLoS One 2013;8(5):e63093.
      doi: 10.1371/journal.pone.0063093pubmed: 23675455google scholar: lookup
    30. Coulstock E, Sosabowski J, Ovečka M, Prince R, Goodall L, Mudd C, Sepp A, Davies M, Foster J, Burnet J, Dunlevy G, Walker A. Liver-targeting of interferon-alpha with tissue-specific domain antibodies. PLoS One 2013;8(2):e57263.
      doi: 10.1371/journal.pone.0057263pubmed: 23451195google scholar: lookup
    31. Noorkhajavi G, Banakholdi A, Torabi A, Zoghi A, Iranijam E, Safarzadeh E. Recent clinical advances in nonconjugated antibodies and antibody-drug conjugates for colorectal cancer treatment. Cancer Cell Int 2025 Nov 10;25(1):395.
      doi: 10.1186/s12935-025-04039-8pubmed: 41214696google scholar: lookup
    32. Narayana RVL, Gupta R. Exploring the therapeutic use and outcome of antibody-drug conjugates in ovarian cancer treatment. Oncogene 2025 Jul;44(28):2343-2356.
      doi: 10.1038/s41388-025-03448-3pubmed: 40514426google scholar: lookup
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