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Antibody-Based Therapeutics for Autoimmune Diseases

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Dr. Naim Mahroum

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Department of Infectious Diseases and Clinical Microbiology, International School of Medicine, Istanbul Medipol University, Kavacık, Göztepe Mah, Atatürk Cd. No: 40, Istanbul 34810, Turkey
Interests: internal medicine; infectious diseases; autoimmune diseases; infection and autoimmunity; COVID-19/viral infections; vaccines

Special Issue Information

Dear Colleagues,

Autoimmune diseases are characterized by the breakdown of immune tolerance, leading to the activation of autoreactive T- and B-cells and subsequent tissue damage. Despite major advances in our understanding of these disease pathogenesis, current therapeutic approaches largely rely on broad immunosuppression, which—in addition to having significant adverse effects—may impair protective immune functions and fail to achieve sustained disease control.

Antibody-based therapeutics have emerged as a central component in the management of autoimmune disorders, offering increased specificity through targeting key immune pathways, including B-cell depletion, cytokine neutralization, and modulation of stimulatory signals. Nevertheless, challenges around immunogenicity, the variety of patient responses, and safety remain critical considerations.

This Special Issue aims to provide a comprehensive overview of the recent advances in antibody-based therapies for autoimmune diseases, covering mechanistic insights, clinical applications, and emerging modalities such as bispecific antibodies, antibody–drug conjugates, and personalized approaches. Emphasis will be placed on precision medicine approaches, including biomarker-driven patient stratification, as well as innovative strategies designed to restore immune tolerance.

By integrating basic, translational, and clinical perspectives, this Special Issue will highlight the current challenges and explore the future directions of more targeted, effective, and personalized therapeutic strategies in autoimmunity.

Dr. Naim Mahroum
Guest Editor

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Review

14 pages, 536 KB

Open AccessReview

Antibody-Based Therapeutics in Autoimmune Diseases: Mechanisms, Challenges, and Future Perspectives

by Naim Mahroum

Int. J. Mol. Sci. 2026, 27(18), 8030; https://doi.org/10.3390/ijms27188030 - 9 Sep 2026

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Abstract

Autoimmune diseases encompass nearly 100 distinct conditions characterized by dysregulated immune responses against self-antigens, resulting in tissue damage, chronic inflammation, and substantial morbidity. Over recent decades, the global burden of autoimmune diseases has increased, while their therapeutic management has undergone a paradigm shift from broad, nonspecific immunosuppression toward targeted biologic therapies. Among these, antibody-based therapeutics, including monoclonal antibodies targeting cytokines, cell-surface molecules, and co-stimulatory pathways, have transformed the treatment of numerous systemic and organ-specific autoimmune disorders. Nevertheless, important challenges remain, including primary non-response, secondary loss of efficacy related to immunogenicity or disease adaptation, increased susceptibility to infections, and mechanistic redundancy among therapeutic targets. This review provides a comprehensive overview of the cellular and molecular mechanisms underlying antibody-based therapies, summarizes major therapeutic target classes across autoimmune diseases, and examines their clinical and mechanistic limitations. Emerging therapeutic platforms, including bispecific antibodies, antibody–drug conjugates (ADCs), novel Fc-engineering, and cellular approaches such as CD19-targeted chimeric antigen receptor (CAR)-T therapy, are also discussed. Finally, antigen-specific immunotherapies designed to restore antigen-specific immune tolerance while preserving systemic host defense are explored. These approaches may represent an important next frontier in the treatment of autoimmune diseases, moving beyond broad systemic immune modulation toward more selective and durable immune control. Full article

(This article belongs to the Special Issue Antibody-Based Therapeutics for Autoimmune Diseases)

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43 pages, 9146 KB

Open AccessReview

Antibody-Drug Conjugates in Solid Tumor Oncology and the Frontier of Precision Immunosuppression: A Mechanistic, Translational, and Clinical Review

by Ibraheem Masoud, Nada Saed Homod Al Shaer, Ahmad Masoud, Ahmad Al Jandali, Abdulrahman Aldahash, Abdullah Jabri, Mohamed Alsharif, Fareeha Arshad, Itika Arora, Mohammed Imran Khan and Ahmed Yaqinuddin

Int. J. Mol. Sci. 2026, 27(12), 5196; https://doi.org/10.3390/ijms27125196 - 9 Jun 2026

Cited by 1 | Viewed by 1747

Abstract

Antibody-drug conjugates (ADCs) have transitioned from clinically marginal agents into a defining therapeutic class for solid tumor oncology. In DESTINY-Breast03, trastuzumab deruxtecan achieved a four-fold progression-free survival advantage over trastuzumab emtansine, attributable not to antibody engineering but to the linker-payload axis: a cleavable peptide linker and a topoisomerase I payload with bystander activity. Sacituzumab govitecan extends the same logic to Trop-2-positive disease via extracellular payload release, and the framework now spans breast, urothelial, gynecologic, lung, gastric, and colorectal cancers, with enfortumab vedotin plus pembrolizumab displacing platinum chemotherapy as first-line therapy for urothelial cancer in EV-302 (median overall survival 31.5 versus 16.1 months). This review synthesizes ADC biology along three analytical axes. The mechanistic axis links each linker-payload-DAR configuration to a specific tumor-biology barrier: vascular limitation, which delivers approximately 0.1% of the administered dose to tumor tissue; the binding-site barrier, which concentrates exposure at the perivascular margin; and antigen mosaicism, which defeats internalization-dependent killing. The translational axis examines resistance as a coordinated failure across antigen modulation, trafficking, efflux, apoptotic execution, and lysosomal processing. The clinical axis traces the platform’s migration toward earlier-line and curative-intent settings. We close by examining whether the ADC delivery architecture translates to precision immunosuppression in autoimmune disease, where the glucocorticoid receptor modulator ADC ABBV-154 met placebo-controlled efficacy endpoints in rheumatoid arthritis but was discontinued because its benefit-risk profile did not differentiate it from existing biologic therapies. Full article

(This article belongs to the Special Issue Antibody-Based Therapeutics for Autoimmune Diseases)

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