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Pharmaceutics
Special Issues
Advancements and Innovations in Antibody Drug Conjugates
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Advancements and Innovations in Antibody Drug Conjugates

A special issue of Pharmaceutics (ISSN 1999-4923). This special issue belongs to the section "Drug Targeting and Design".

Deadline for manuscript submissions: 30 November 2025 | Viewed by 1055

Special Issue Editors

Dr. Murali Mohan Yallapu

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Guest Editor
Department of Immunology and Microbiology, College of Medicine, University of Texas Rio Grade Valley, McAllen, TX 78503, USA
Interests: cancer therapy; drug delivery; drug targeting; infectious disease; micelle; nanoparticles; nanotechnology; polymers; targeted therapies; HIV; antibody engineering; antibody–drug conjugates
Special Issues, Collections and Topics in MDPI journals
Dr. Shivaji Edupuganti

E-Mail Website
Guest Editor
Center for Cancer Research, National Cancer Institute, NIH, Frederick, MD 21702, USA
Interests: C-H activation; self-immolative linkers; antibody drug conjugates; organic chemistry
Dr. Ebaston Thankarajan

E-Mail Website
Guest Editor
Center for Cancer Research, National Cancer Institute, NIH, Frederick, MD 21702, USA
Interests: medicinal chemistry; antibody drug conjugates; fluorescence imaging; targeted drug delivery; photodynamic therapy

Special Issue Information

Dear Colleagues,

Antibody–drug conjugates (ADCs) represent a groundbreaking advancement in targeted cancer therapy, merging the specificity of monoclonal antibodies with a highly potent cytotoxic small-molecule drug. ADCs aim to improve efficacy by reducing side effects through the specific targeting of cancer cells, sparing healthy tissues. Recent innovations in ADC development have focused on optimizing antibody engineering, bispecific antibodies, combination therapies, linker stability, and the choice of payloads to enhance the therapeutic index. Improved conjugation techniques, payload delivery mechanisms, and linker chemistries are advancing the field towards greater efficacy and safety profiles.

This Special Issue highlights the latest advancements and innovations in ADC technology including recent antibody-based drug delivery systems, approved ADCs, clinical development, cytotoxic payload, drug linker design, cleavable linker design, site-specific conjugation, biodistribution, pharmacokinetics, and molecular imaging.

Dr. Murali Mohan Yallapu
Dr. Shivaji Edupuganti
Dr. Ebaston Thankarajan
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 100 words) can be sent to the Editorial Office for announcement on this website.

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-blind 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 conjugates
  • monoclonal antibodies
  • targeted therapies
  • linker technologies
  • site-specific conjugation
  • bioimaging
  • pharmacokinetics
  • therapeutic index
  • next-generation ADCs
  • drug resistance
  • bispecific antibodies
  • combination therapies
  • off-target toxicity
  • efficacy and safety
  • tumor-specific antigens

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Published Papers (1 paper)

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Research

19 pages, 2002 KiB  
Article
A Dual-Payload Bispecific ADC Improved Potency and Efficacy over Single-Payload Bispecific ADCs
by Nicole A. Wilski, Peter Haytko, Zhengxia Zha, Simin Wu, Ying Jin, Peng Chen, Chao Han and Mark L. Chiu
Pharmaceutics 2025, 17(8), 967; https://doi.org/10.3390/pharmaceutics17080967 - 25 Jul 2025
Viewed by 650
Abstract
Background/Objectives: All current FDA-approved antibody–drug conjugates (ADCs) are single-target and single-payload molecules that have limited efficacy in patients due to drug resistance. Therefore, our goal was to generate a novel ADC that was less susceptible to single points of resistance to reduce the [...] Read more.
Background/Objectives: All current FDA-approved antibody–drug conjugates (ADCs) are single-target and single-payload molecules that have limited efficacy in patients due to drug resistance. Therefore, our goal was to generate a novel ADC that was less susceptible to single points of resistance to reduce the likelihood of patient relapse. Methods: We developed a dual-targeting, dual-payload ADC by conjugating a bispecific EGFR x cMET antibody to two payloads (MMAF and SN38) that had separate mechanisms of action using a novel tri-functional linker. This dual-payload ADC was tested for potency and efficacy in dividing and nondividing in vitro cell models using multiple tumor cell types. Efficacy of the dual-payload ADC was confirmed using in vivo models. Results: Our ADC with dual MMAF and SN38 payloads was more efficacious in inhibiting cell proliferation than single-payload ADCs across multiple cancer cell lines. In addition, the dual-payload molecule inhibited nondividing cells, which were more resistant to traditional ADC payloads. The dual-payload ADC also exhibited more potent tumor growth inhibition in vivo compared to that of single-payload ADCs. Conclusions: Overall, the bispecific antibody conjugated with both the MMAF and SN38 payloads inhibited tumor growth more strongly than ADCs conjugated with MMAF or SN38 alone. Developing dual-payload ADCs could limit the impact of acquired resistance in patients as well as lower the effective dose of each payload. Full article
(This article belongs to the Special Issue Advancements and Innovations in Antibody Drug Conjugates)
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