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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

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