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12.5
6.9
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Pharmaceutics
Special Issues
Antibody–Drug Conjugates Therapeutics
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Antibody–Drug Conjugates Therapeutics

A special issue of Pharmaceutics (ISSN 1999-4923). This special issue belongs to the section "Biologics and Biosimilars".

Deadline for manuscript submissions: 31 January 2027 | Viewed by 7181

Editors

Prof. Dr. Amal Ali Elkordy

E-Mail Website
Guest Editor
School of Pharmacy and Pharmaceutical Sciences, Faculty of Health Sciences and Wellbeing, University of Sunderland, Sunderland SR1 3SD, UK
Interests: monoclonal antibodies and other protein formulations; solid dosage forms; formulation of gene therapeutics; liposomal drug delivery systems
Special Issues, Collections and Topics in MDPI journals
Dr. Summer Y. Y. Ha

E-Mail Website
Guest Editor
Texas Therapeutics Institute, The Brown Foundation Institute of Molecular Medicine, The University of Texas Health Science Center at Houston, Houston, TX, USA
Interests: antibody–drug conjugates; glioblastoma multiforme; breast cancer; protein chemistry; drug delivery

Special Issue Information

Dear Colleagues,

Antibody–drug conjugates (ADCs) are a promising class of cancer therapeutics. These conjugates consist of a monoclonal antibody linked to cytotoxic agents through chemical linkers. By leveraging the high specificity of monoclonal antibodies, ADCs enable precise drug delivery to target tissues, thereby enhancing the overall therapeutic index. The development of ADCs, however, is complex and faces numerous challenges, such as antigen selection, linker stability, drug resistance, and toxicity management. This Special Issue will focus on recent advancements in ADC design. Topics will include novel conjugation techniques, innovative payloads, improved linker technologies, and next-generation ADC platforms. Additionally, this Special Issue will explore mechanisms of action, clinical applications, and strategies to enhance therapeutic efficacy. Contributions on combination therapies, bispecific ADCs, and applications beyond oncology are also welcome. Both original research papers and comprehensive review articles are encouraged to contribute to the evolving landscape of ADC-based therapeutics.

We look forward to receiving your valuable contributions.

Prof. Dr. Amal Ali Elkordy
Dr. Summer Y. Y. Ha
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 250 words) can be sent to the Editorial Office for assessment.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-anonymized peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Pharmaceutics is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • antibody–drug conjugate
  • drug delivery
  • antibody
  • payload
  • linker
  • protein conjugation

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Published Papers (3 papers)

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Research

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16 pages, 1875 KB  
Article
Structural Characterization of Linker Shielding in ADC Site-Specific Conjugates
by Maru Jaime-Garza, Andrew Waight, Manish Hudlikar, Michael J. Eddins, Elnaz S. Rasti, Jan Paulo T. Zaragoza, Laurence Fayadat-Dilman, Jill E. Chrencik, Sandra B. Gabelli, Yun-Ting Chen and Cameron L. Noland
Pharmaceutics 2025, 17(12), 1568; https://doi.org/10.3390/pharmaceutics17121568 - 5 Dec 2025
Cited by 2 | Viewed by 3381
Abstract
Background/Objectives: Antibody–Drug Conjugates (ADCs) have rapidly evolved from early, rudimentary conjugates to highly targeted and precisely engineered molecules. Despite notable clinical successes, ADCs continue to face significant challenges, including aggregation and high hydrophobicity driven by high drug-to-antibody ratios (DARs), premature payload release, [...] Read more.
Background/Objectives: Antibody–Drug Conjugates (ADCs) have rapidly evolved from early, rudimentary conjugates to highly targeted and precisely engineered molecules. Despite notable clinical successes, ADCs continue to face significant challenges, including aggregation and high hydrophobicity driven by high drug-to-antibody ratios (DARs), premature payload release, dose-limiting toxicities, and suboptimal pharmacokinetics. While site-specific linker–payload conjugation has improved ADC homogeneity and stability, the structural basis of antibody–linker interactions at specific sites remains underexplored. Methods: In this work, we present the crystal structures of trastuzumab Fab and Fc domains site-specifically conjugated with a cleavable linker–payload. Results: Our findings suggest that pockets within both Fab and Fc regions may interact with and shield the linker portion of the conjugate. Conclusions: These insights highlight the previously underappreciated potential of structure-based design to drive the optimization of ADC linker chemistry and facilitate the co-design of bespoke linker–payloads tailored to individual antibody conjugation sites. Full article
(This article belongs to the Special Issue Antibody–Drug Conjugates Therapeutics)
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Review

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32 pages, 2337 KB  
Review
Antibody–Drug Conjugates: Pharmacotherapeutic Properties and Future Perspectives
by André Augusto, Maria L. S. Cristiano and Jaime Conceição
Pharmaceutics 2026, 18(4), 468; https://doi.org/10.3390/pharmaceutics18040468 - 12 Apr 2026
Cited by 1 | Viewed by 1565
Abstract
Background: The clinical landscape for antibody–drug conjugates (ADCs) is currently experiencing an unprecedented expansion, with more than 20 agents approved to date and hundreds presently under clinical evaluation, underscoring their growing impact in precision oncology. By combining the cytotoxic potency of chemotherapy with [...] Read more.
Background: The clinical landscape for antibody–drug conjugates (ADCs) is currently experiencing an unprecedented expansion, with more than 20 agents approved to date and hundreds presently under clinical evaluation, underscoring their growing impact in precision oncology. By combining the cytotoxic potency of chemotherapy with the selectivity of monoclonal antibodies, ADCs have redefined targeted cancer therapy. Nevertheless, challenges related to toxicity, resistance, and suboptimal drug delivery continue to limit their full clinical potential. Objectives: This review provides a comprehensive description of currently approved ADCs, with a particular focus on their pharmacotherapeutic properties, mechanisms of action, therapeutic indications, and safety profiles. By integrating currently available clinical data and pharmacological properties, it is possible to identify key translational gaps between ADC design and their real-world performance. This article also evaluates how the structural components contribute to both efficacy and toxicity of ADCs, offering a framework for rational molecular optimizations. Conclusions: Beyond the current oncology-centric paradigm, this review highlights the imminent pivot toward non-oncology applications, including targeted therapies for autoimmune, infectious, and neurodegenerative diseases. Importantly, this article highlights emerging innovations shaping the next generation of ADCs, including bispecific antibodies, novel cytotoxic payloads with improved therapeutic indices, and advanced linker technologies enabling more precise payload release. Despite current limitations, ongoing advances in ADC development, along with a rapidly expanding clinical pipeline, position these drugs in a dynamic therapeutic class with the potential to transform multiple complex diseases and improve the quality of life of patients who have them. Full article
(This article belongs to the Special Issue Antibody–Drug Conjugates Therapeutics)
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25 pages, 4105 KB  
Review
Structural and Functional Insights into Viral and Fungal Proteins Involved in Chronic Inflammation and Their Biologic Treatments
by Mohamed Halawa, Alicia L. Gallo and Valerie J. Carabetta
Pharmaceutics 2025, 17(11), 1466; https://doi.org/10.3390/pharmaceutics17111466 - 13 Nov 2025
Viewed by 1434
Abstract
Chronic inflammation constitutes a significant characteristic of sustained infections caused by viral and fungal pathogens, with a strong correlation to the development of cancer, autoimmune disorders, and tissue fibrosis. Viral proteins such as HIV-1 Tat, HBV X (HBx), HPV E6/E7, and EBV LMP1 [...] Read more.
Chronic inflammation constitutes a significant characteristic of sustained infections caused by viral and fungal pathogens, with a strong correlation to the development of cancer, autoimmune disorders, and tissue fibrosis. Viral proteins such as HIV-1 Tat, HBV X (HBx), HPV E6/E7, and EBV LMP1 modulate the host’s immune signaling pathways, primarily through the activation of the NF-κB signaling cascade and the disruption of cytokine equilibrium. These molecular interactions result in a pro-inflammatory microenvironment that facilitates viral persistence, immune evasion, and the process of oncogenesis. Structural investigations have elucidated the mechanisms by which these viral proteins interact with host signaling complexes, thereby highlighting their potential as viable therapeutic targets. Similarly, fungal proteins, including secreted aspartyl proteases (Saps), ribotoxin Asp f1, and chitin-binding proteins, incite chronic inflammation by activating pattern recognition receptors and triggering inflammasome activation. Despite the limited structural information of these fungal proteins, emerging models and bioinformatic analyses identified conserved motifs that are crucial for host interactions. Biologic therapies, encompassing antiviral and antifungal peptides as well as monoclonal antibodies, are currently under development to disrupt these protein-host interactions and modulate inflammatory responses. This review provides structural and functional insight into viral and fungal inflammatory proteins and evaluates the potential of biologics as targeted therapeutic interventions for chronic inflammation associated with infections. We discuss the ongoing clinical trials involving neutralizing antibodies targeting HIV, peptide vaccines aimed at HPV and other promising molecules. Finally, we discuss the current limitations of biologics and possible solutions to translate these promising therapeutics into clinical practice. Full article
(This article belongs to the Special Issue Antibody–Drug Conjugates Therapeutics)
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