Antibody-Drug Conjugates—a Coming of Age

A special issue of Cancers (ISSN 2072-6694).

Deadline for manuscript submissions: closed (28 April 2023) | Viewed by 12239

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Guest Editor
King's College London, Institute of Pharmaceutical Science, School of Cancer & Pharmaceutical Sciences, Faculty of Life Sciences & Medicine, Franklin–Wilkins Building, London SE1 9NH, UK
Interests: discovery of novel anticancer therapies, especially those based on natural products; antibody–drug conjugates (ADCs); anticancer agents that work through a DNA-interactive mechanism
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Dear Colleagues,

Antibody-Drug Conjugates (ADCs) have finally come of age, with fifteen examples approved world-wide, seven by the FDA alone between 2019–2022. Furthermore, there are currently over 100 ADCs in clinical trials, with further approvals anticipated in the near future. In particular, ADCs such as trastuzumab deruxtecan-nxki (Enhertu®) have made a significant difference to the lives of cancer patients, as evidenced by clinical results recently announced at the 2022 ASCO conference (i.e., reducing the risk of progression or death in HER2-low metastatic breast cancer by 49% vs. chemotherapy). To celebrate this success, we are pleased to invite you to submit manuscripts for a Special Issue of the journal Cancers, which will focus on cutting edge ADC research and development. In this Special Issue, both original research articles and reviews are welcome, and research areas may include (but are not limited to) targeting strategies, antibody/linker/payload design, and safety issues relating to ADCs. I look forward to receiving your contributions.

Prof. Dr. David E. Thurston
Guest Editor

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Keywords

  • antibody–drug conjugates, ADCs
  • targeted cancer therapy
  • antigens
  • antibodies
  • monoclonal antibodies
  • payloads
  • warheads
  • chemical linkers

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Published Papers (2 papers)

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Review

23 pages, 676 KiB  
Review
Belantamab Mafodotin: From Clinical Trials Data to Real-Life Experiences
by Sonia Morè, Massimo Offidani, Laura Corvatta, Maria Teresa Petrucci and Francesca Fazio
Cancers 2023, 15(11), 2948; https://doi.org/10.3390/cancers15112948 - 27 May 2023
Cited by 7 | Viewed by 3391
Abstract
Despite the recent approval of novel immunotherapies, such as immunomodulatory drugs, proteasome inhibitors and anti-CD38 monoclonal antibodies, Multiple Myeloma (MM) remains incurable, and the acquisition of triple-refractoriness leads to really dismal outcomes in even earlier lines of therapy. More recently, innovative therapeutic strategies [...] Read more.
Despite the recent approval of novel immunotherapies, such as immunomodulatory drugs, proteasome inhibitors and anti-CD38 monoclonal antibodies, Multiple Myeloma (MM) remains incurable, and the acquisition of triple-refractoriness leads to really dismal outcomes in even earlier lines of therapy. More recently, innovative therapeutic strategies targeting B cell maturation antigen (BCMA), highly expressed on the plasma cell surface, are drawing different future landscapes in terms of effectiveness and outcomes. Belantamab Mafodotin, a first-in-class anti-BCMA antibody–drug conjugate, demonstrated good efficacy and safety profile in triple-refractory patients in the phase 2 DREAMM-2 trial, and it was approved for the treatment of MM triple-exposed patients with >4 prior lines of therapy. Here, starting from Belantamab Mafodotin clinical trials and also exploring combination studies and different schedules in order to improve its efficacy and toxicity, we focused on real-life experiences all over the world, which have confirmed clinical trial data and encourage further Belantamab Mafodotin investigations. Full article
(This article belongs to the Special Issue Antibody-Drug Conjugates—a Coming of Age)
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37 pages, 2181 KiB  
Review
Target Antigen Attributes and Their Contributions to Clinically Approved Antibody-Drug Conjugates (ADCs) in Haematopoietic and Solid Cancers
by Benjamina Esapa, Jiexuan Jiang, Anthony Cheung, Alicia Chenoweth, David E. Thurston and Sophia N. Karagiannis
Cancers 2023, 15(6), 1845; https://doi.org/10.3390/cancers15061845 - 19 Mar 2023
Cited by 32 | Viewed by 7603
Abstract
Antibody drug conjugates (ADCs) are powerful anti-cancer therapies comprising an antibody joined to a cytotoxic payload through a chemical linker. ADCs exploit the specificity of antibodies for their target antigens, combined with the potency of cytotoxic drugs, to selectively kill target antigen-expressing tumour [...] Read more.
Antibody drug conjugates (ADCs) are powerful anti-cancer therapies comprising an antibody joined to a cytotoxic payload through a chemical linker. ADCs exploit the specificity of antibodies for their target antigens, combined with the potency of cytotoxic drugs, to selectively kill target antigen-expressing tumour cells. The recent rapid advancement of the ADC field has so far yielded twelve and eight ADCs approved by the US and EU regulatory bodies, respectively. These serve as effective targeted treatments for several haematological and solid tumour types. In the development of an ADC, the judicious choice of an antibody target antigen with high expression on malignant cells but restricted expression on normal tissues and immune cells is considered crucial to achieve selectivity and potency while minimising on-target off-tumour toxicities. Aside from this paradigm, the selection of an antigen for an ADC requires consideration of several factors relating to the expression pattern and biological features of the target antigen. In this review, we discuss the attributes of antigens selected as targets for antibodies used in clinically approved ADCs for the treatment of haematological and solid malignancies. We discuss target expression, functions, and cellular kinetics, and we consider how these factors might contribute to ADC efficacy. Full article
(This article belongs to the Special Issue Antibody-Drug Conjugates—a Coming of Age)
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