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Antibody Engineering and Therapeutic Applications
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Antibody Engineering and Therapeutic Applications

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pharmacology".

Deadline for manuscript submissions: 20 September 2026 | Viewed by 13196

Editor

Prof. Dr. Yong-Seok Heo

E-Mail Website
Guest Editor
Department of Chemistry, Konkuk University, 120 Neungdong-ro, Gwangjin-gu, Seoul 05029, Republic of Korea
Interests: therapeutic antibody; cancer immunotherapy; antibody engineering; structure and mechanism of antibody drugs; protein structure
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Recent advances in antibody-mediated therapies have markedly enhanced their clinical efficacy. Cancer immunotherapy has drastically altered the treatment of multiple types of tumors, leading to the approval of monoclonal antibodies for checkpoint inhibition, CAR-T cell therapies, T-cell engagers, and bispecific antibod-ies. Antibody-drug conjugates (ADCs) represent one of the most swiftly blooming therapeutic modalities in oncology, with 12 ADCs approved by the FDA and over 300 currently undergoing clinical investigations. 

The design and clinical application of monoclonal antibody (mAb) therapeutics ne-cessitate thoroughly comprehending the intricate relationship between their struc-ture and function. Recent breakthroughs in artificial intelligence (AI) methodologies have made significant progress in the generation of protein sequences and struc-tures, enabling the de novo design of antibodies capable of binding to specific sur-faces of target proteins. 

This Special Issue aims to address recent advancements and innovative concepts in the design and application of cutting-edge antibody-mediated therapies, including but not limited to mAb therapeutics, biosimilars, antibody-drug conjugates (ADCs), bispecific and multispecific antibodies, T-cell engagers (TCEs), CAR-T or CAR-NK therapies, nanobodies, immunocytokines, antibody-targeted nanoparticles, antibody structure and mechanism of action, antibody engineering, and AI-driven antibody design. Original papers and review articles are welcome.

Prof. Dr. Yong-Seok Heo
Guest Editor

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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. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

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Keywords

  • monoclonal antibody (mAb) therapies
  • antibody engineering
  • antibody-drug conjugate (ADC)
  • chimeric antigen receptor T cell (CAR-T)
  • bispecific antibody
  • T-cell engager (TCE)
  • cancer immunotherapy
  • immunocytokine
  • AI-driven antibody design
  • antibody structure and mechanism of action

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Published Papers (3 papers)

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Review

30 pages, 1107 KB  
Review
Targeted Therapy in Hepatobiliary Pancreatic Cancer (HPC): Advantages and Advancements of Antibody Drug Conjugates, a Type of Chemo-Biologic Hybrid Drugs
by Tushar Deb Nath, Attrayo Mukherjee, Subhash C. Chauhan and Debasish Bandyopadhyay
Int. J. Mol. Sci. 2026, 27(6), 2707; https://doi.org/10.3390/ijms27062707 - 16 Mar 2026
Viewed by 1520
Abstract
Currently, there are very few efficient treatment options for hepatobiliary pancreatic cancer (HPC), which comprises pancreatic ductal adenocarcinoma (PDAC), biliary tract cancer (BTC), and hepatocellular carcinoma (HCC). The HPC tumors are the most lethal malignant tumors in the world. Traditional chemotherapy offers little [...] Read more.
Currently, there are very few efficient treatment options for hepatobiliary pancreatic cancer (HPC), which comprises pancreatic ductal adenocarcinoma (PDAC), biliary tract cancer (BTC), and hepatocellular carcinoma (HCC). The HPC tumors are the most lethal malignant tumors in the world. Traditional chemotherapy offers little survival benefit and is associated with notable systemic toxicity, which has made antibody–drug conjugates (ADCs) a hopeful treatment option. Strong cytotoxic drugs combine with monoclonal antibodies to attack tumor-associated antigens. This review discusses the benefits and current developments of Antibody–Drug Conjugates (ADCs) in treating HPC. It also covers their mechanisms of action, ongoing clinical trials, and the challenges of targeting specific antigens like B7-H3, c-MET, and Trop-2. ADCs deliver chemotherapy directly to cancer cells while protecting healthy tissues. It also addresses the favorable outcomes of several preclinical and clinical studies and highlights future paths to enhance ADC efficacy, including addressing tumor heterogeneity, overcoming resistance, and optimizing drug-delivery techniques. This approach has the possibility to further increase patient survival and minimize side effects in HPC patients. To the best of our knowledge and based on the available literature, we have made every effort to include all relevant publications; any inadvertent omissions are entirely unintentional. Full article
(This article belongs to the Special Issue Antibody Engineering and Therapeutic Applications)
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23 pages, 1541 KB  
Review
Characterization of Conformational Instability of Monoclonal Antibodies During Chromatographic Purification
by Krystian Baran and Rafał Podgórski
Int. J. Mol. Sci. 2026, 27(4), 2064; https://doi.org/10.3390/ijms27042064 - 23 Feb 2026
Viewed by 1497
Abstract
Monoclonal antibodies represent one of the fastest-growing sectors of the biopharmaceutical industry. Their high therapeutic efficacy and reduced incidence of adverse effects compared to conventional therapies have led to an increasing demand for these products. The costliest stages of monoclonal antibody production are [...] Read more.
Monoclonal antibodies represent one of the fastest-growing sectors of the biopharmaceutical industry. Their high therapeutic efficacy and reduced incidence of adverse effects compared to conventional therapies have led to an increasing demand for these products. The costliest stages of monoclonal antibody production are the separation and purification processes, which underscores the need for continuous development and optimization of applied methodologies. Active pharmaceutical ingredients must exhibit high purity and preserved biological activity in order to meet stringent regulatory requirements. Macromolecules such as monoclonal antibodies possess complex conformational structures that significantly influence their stability. The application of multi-step chromatographic processes during purification from cell culture harvests may induce structural alterations, including protein unfolding and aggregation, ultimately resulting in decreased product quality and therapeutic effectiveness. Such structural changes may also increase immunogenicity risk and reduce product shelf life, posing additional challenges for downstream processing. In addition, chromatographic media create microenvironments that differ markedly from bulk solution (e.g., high local protein concentration, confined pore spaces and heterogeneous surface chemistry). These effects can promote either self-association driven by colloidal interactions or partial unfolding followed by irreversible aggregation, depending on the unit operation and operating window. Practical mitigation is therefore rarely achieved by a single lever; instead, it requires an integrated view of resin selection, buffer composition (pH, salt type and ionic strength, and stabilizing additives), residence time and temperature, as well as an analytics strategy that combines orthogonal aggregation assays with structural probes. This work discusses the phenomena of unfolding and aggregation of therapeutic proteins, with particular emphasis on monoclonal antibodies occurring during chromatographic purification. Furthermore, key analytical methods, characterization techniques, and mitigation strategies aimed at improving product quality and reducing manufacturing costs are reviewed. Full article
(This article belongs to the Special Issue Antibody Engineering and Therapeutic Applications)
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15 pages, 1090 KB  
Review
Technologies for Monoclonal Antibody Discovery and Development
by Kyung Ho Han, Yi-Chuan Li, Rabia Parveen, Srimathi Venkataraman and Chih-Wei Lin
Int. J. Mol. Sci. 2025, 26(21), 10470; https://doi.org/10.3390/ijms262110470 - 28 Oct 2025
Cited by 5 | Viewed by 9664
Abstract
Monoclonal antibodies (mAbs) represent one of the most successful classes of biopharmaceuticals, with more than 100 approved for treating oncological, immunological, and infectious diseases. Antibody discovery and development have been driven by diverse methodologies. Classical strategies such as mouse hybridoma technology, phage display, [...] Read more.
Monoclonal antibodies (mAbs) represent one of the most successful classes of biopharmaceuticals, with more than 100 approved for treating oncological, immunological, and infectious diseases. Antibody discovery and development have been driven by diverse methodologies. Classical strategies such as mouse hybridoma technology, phage display, transgenic mouse models, and single B cell isolation have enabled the generation of high-affinity therapeutic antibodies. Beyond binding affinity, recent innovations in combinatorial antibody libraries have facilitated the selection of functional antibodies within cellular environments, revealing their ability to act as agonists or antagonists and influence signal transduction pathways. These insights expand therapeutic applications by enabling modulation of complex cellular responses. Recent breakthroughs in artificial intelligence, involving antibody generation supported by rapidly growing antibody sequence and structure databases, are transforming computational protein design. This review highlights five major approaches (hybridoma technology, phage display, transgenic mouse models, and single B cell isolation, de novo antibody design) for antibody discovery and development. These approaches offer innovative strategies designed to accelerate the discovery process and enhance therapeutic outcomes for human diseases. Full article
(This article belongs to the Special Issue Antibody Engineering and Therapeutic Applications)
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