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A Global Overview of Therapeutic Antibody Development
Biointron2025-03-12Read time: 8 mins
Image credit: Dana-Farber Cancer Institute
Clinical Advancements in Monoclonal Antibody Therapy
Monoclonal antibodies (mAbs) have significantly improved the treatment landscape for various diseases, particularly in inflammatory bowel disease (IBD), which includes Crohn’s disease and ulcerative colitis. Research into integrin-blocking biologics has shown its potential as precision treatments for IBD, which affects over 6.8 million people worldwide, and its prevalence continues to rise. To improve patient outcomes, optimizing the timing of biologic therapy initiation, identifying patients most likely to benefit from specific treatments, and exploring dual advanced therapies are beneficial. Combining biologic agents may help overcome the efficacy limitations of monotherapy, potentially redefining the current treatment paradigm.
B-cell screening has emerged as a key technology in antibody discovery, allowing the capture of an individual's B-cell repertoire into immortalized B-cell libraries. These libraries enable high-throughput screening to identify antibodies with desirable binding and functional properties.
Such an approach is particularly valuable for discovering novel antigens relevant to oncology and infectious diseases. Studying B-cell repertoires from exceptional responders—patients who exhibit extraordinary immune responses—can yield new therapeutic insights. Furthermore, large-scale patient databases generated from these studies could enhance understanding of functional immune responses, leading to improved antibody-based therapies.
Antibody therapies have become standard treatments in oncology and beyond. There is a need for next-generation antibodies with improved safety and efficacy, emphasizing first-in-class and best-in-class biologics. While antibody-drug conjugates (ADCs) and T-cell engagers (TCEs) have validated new mechanisms of action, identifying novel antigen targets remains a frontier. The ability to discover and validate unique disease-associated antigens will be pivotal in shaping future therapeutic strategies.
The global market for antibody therapeutics is poised for substantial growth, with projections estimating to grow at a robust CAGR of 14.5%, reaching US$252.6 billion in 2024 and an impressive US$497.5 billion by 2029. The expansion of biologics is accompanied by the challenge of impending patent expirations for key therapies. There is an increasing demand for treatments with improved safety and efficacy profiles, which is expected to grow as patient needs rise. Furthermore, the ability to respond quickly to emerging infectious diseases, such as COVID-19 and potential future pandemics, remains a critical consideration. The success of anti-infective antibodies, such as those targeting viral and bacterial threats, presents a significant opportunity to develop similar therapeutics.
In parallel, advancements in antibody-drug conjugates (ADCs) are progressing, particularly with the refinement of cytotoxic payloads. One promising strategy involves using amanitin, a potent toxin derived from the death cap mushroom, as a payload. Amanitin works by targeting the transcription process essential to eukaryotic cell survival, making it distinct from other cytotoxic agents. This innovative approach offers new possibilities for treating resistant cancers.
Main functions of therapeutic monoclonal antibodies (mAbs). DOI: 10.3390/pharmaceutics12010062
The Rising Prominence of ADCs
Antibody-drug conjugates have gained increasing attention within the pharmaceutical industry due to their targeted approach to cancer therapy. The specificity of monoclonal antibodies, combined with the cytotoxic potency of their payloads, has contributed to the success of recent ADC approvals. Advancements in linker technology and payload selection have addressed previous limitations, improving ADC stability and efficacy.
Tumor biology research plays a crucial role in identifying new cancer-specific targets, which is driving the continued development of antibody-drug conjugates (ADCs). Combining ADCs with other therapeutic strategies such as immune checkpoint inhibitors, kinase inhibitors, or chemotherapy may improve their therapeutic efficacy. By integrating multiple treatment modalities, ADC-based therapies could potentially overcome tumor resistance mechanisms and enhance patient outcomes.
In the field of precision oncology, ADC technology is expected to have a significant long-term impact. ADCs are designed to minimize off-target toxicity while delivering potent therapeutic agents directly to tumor cells. Future advancements in ADC technology could further optimize their therapeutic index, making cancer treatments more effective and better tolerated by patients.
Multifunctional Antibodies: Bivalent and trivalent antibodies promote proximity-based biological effects, enhancing immune system engagement.
Armed Antibodies: ADCs and radiotherapeutics are expanding the capabilities of antibody-based treatments by incorporating cytotoxic or radiolabeled payloads.
Nanocarrier-Directed Antibodies: Lipid nanoparticles, exosomes, and extracellular vesicles are being explored as antibody delivery systems to enhance stability and tissue targeting.
Artificial intelligence (AI) and machine learning are also beginning to shape antibody design. AI-generated monoclonal antibodies have entered clinical trials, though Jones cautions that the complexity of optimizing multiple therapeutic parameters requires a measured approach. The integration of computational tools into antibody discovery could accelerate the development process and improve therapeutic precision.
Antibodies targeting autoantibodies offer a novel approach for treating rare autoimmune diseases. In the case of immune thrombocytopenia (ITP), this strategy has the potential to revolutionize treatment. ITP is characterized by platelet destruction caused by autoantibodies, which leads to bleeding complications. By selectively targeting plasma cells that produce these autoantibodies, therapeutic antibodies could directly address the root cause of the disease, offering a more effective treatment option.
This strategy aligns with broader efforts to develop antibody therapies for autoimmune conditions. Monoclonal antibodies capable of modulating immune responses are being explored for diseases such as lupus, multiple sclerosis, and myasthenia gravis. These therapies offer targeted interventions that could reduce disease activity while minimizing immunosuppression-related risks.
Advancements in GPCR-Targeting Antibodies
US FDA-approved anti-GPCR antibodies erenumab and mogamulizumab. DOI: 10.3390/ijms21218240
G protein-coupled receptors (GPCRs) are complex drug targets due to their intricate structure and membrane-bound nature. Recent breakthroughs, as described by Miao Li from Bio-Rad Laboratories, have made it possible to develop antibodies targeting GPCRs. Innovations in structural stabilization techniques and advancements in antibody phage display technology have enhanced the feasibility of targeting GPCRs for therapeutic purposes, opening new avenues for treatment.
Phage display technology also facilitates animal-free antibody selection, aligning with industry efforts toward more sustainable and ethical drug discovery approaches. Additionally, bispecific antibodies—capable of engaging two targets simultaneously—are gaining traction, particularly in oncology. These dual-targeting molecules offer the potential for enhanced efficacy and reduced drug resistance, further expanding the therapeutic landscape for antibody-based treatments.
Looking ahead, continued integration of computational tools, artificial intelligence, and high-throughput screening will drive antibody discovery. Advances in these areas will enable more precise target selection and open new avenues for addressing previously undruggable targets, reinforcing the central role of antibodies in modern therapeutic development.
