Driving Innovation in Antibody Therapeutics, From Basic Research to the Clinic

Nearly 25 years after the first FDA-approved antibody-drug conjugate (ADC), the field of antibody therapeutics continues to evolve. Advances in antibody development and engineering, as well as transformative progress in our understanding of biological processes and disease etiology, have unlocked new possibilities. This, in turn, has fueled an exponential surge of excitement and investment in the industry – the global ADC market grew from an estimated $1.4 billion in 2016 to over $11 billion by the end of 2023.¹

While the field has largely been focused on the treatment of hematological malignancies, antibody-based therapeutics are now under development for solid tumors, autoimmune diseases, and other indications. Through continued innovation in antibody engineering, as well as strong supplier partnerships that support research at every level, ADCs, bispecific antibodies, and other therapeutic modalities can reach their full potential. This article will outline the current state of these innovative antibody-based drugs, the technological advances making progress possible, and what the future holds for antibody therapeutics.

A Groundbreaking Class of Therapeutics

Antibody-drug conjugates have taken center stage in cancer drug development, with 13 ADCs approved by the FDA thus far and over 100 candidates currently undergoing clinical trials.² ADCs are engineered to combine the targeted delivery capabilities of monoclonal antibodies with the potency of cytotoxic drugs, addressing the challenges of traditional chemotherapy by pinpointing drug delivery to cancer cells while sparing healthy tissues. While they have shown great promise thus far, a growing body of research efforts are aimed at overcoming persistent challenges with these drugs, improving their performance, and exploring new avenues for therapeutic design. Among the most pressing goals for ADC research are minimizing off-target effects, refining the conjugation process, and maximizing stability in the bloodstream. Researchers are addressing these hurdles with more selective targeting mechanisms, enhanced linker technologies, and site-specific conjugation techniques that improve the stability and delivery of the drug payload.

In addition to ADCs, bispecific and multispecific antibody formats are revolutionizing therapeutic strategies by targeting multiple antigens or epitopes. These therapies enable antibodies to simultaneously bind two or more targets, opening new pathways to engage the immune system directly in tumor destruction. For example, one primary mechanism of action for bispecific antibodies leverages simultaneous targeting of a tumor-associated antigen and an immune cell antigen. This binding brings immune cells, such as T cells, into proximity with cancer cells to enhance the immune response and boost tumor cell killing. Similarly, multispecific antibodies are being developed to address cancer heterogeneity, reducing the likelihood of treatment resistance by simultaneously targeting multiple tumor antigens. Combined with ADCs, these next-generation formats are extending the versatility of antibody therapeutics and improving treatment outcomes, particularly when used alongside immune checkpoint inhibitors and other cancer therapies.

However, the therapeutic utility of ADCs, bispecifics, and other antibody modalities is far from limited to cancer. Beyond oncology, ADCs, bispecifics, and multispecifics are showing promise in treating a wide range of non-cancer indications, including autoimmune diseases, infectious diseases, and even rare genetic disorders. The 2017 approval of emicizumab, a bispecific antibody for the treatment of hemophilia A, marked the first non-cancer indication of a bispecific.³ In autoimmune conditions, bispecific and multispecific antibodies can be designed to selectively target immune cells, such as B and T cells, which drive disease pathology, while sparing healthy immune cells. This targeted approach allows for greater precision in modulating the immune response to potentially reduce side effects associated with conventional immunosuppressive therapies.⁴ ADCs, traditionally used for delivering cytotoxic drug payloads, are also being adapted for non-cancer indications by linking antibodies with immunomodulatory agents or gene-silencing drugs to inhibit disease-causing pathways in a highly targeted manner. With powerful capabilities to precisely engineer structure and function, researchers can continue to optimize antibody therapeutics and explore novel targets and mechanisms of action.

The Continued Impact of Recombinant Antibody Technology

The advent of genetic engineering approaches and the subsequent rise of recombinant antibody technology were foundational in driving progress in antibody therapeutics. Recombinant antibody technology overcomes many of the constraints of hybridoma-based antibody production, making the biopharma space quick to adopt recombinant methods. Its advantages extend beyond the capacity for precise, highly controlled engineering of antibody structure and function – recombinant technology strengthens the quality and reproducibility of experiments at every level, from basic academic research to optimizing therapeutic candidates.

While recombinant technology involves directly manipulating the genes responsible for an antibody’s variable regions and expressing them in host cells to produce antibodies, hybridomas are the result of fusing antibody-producing B cells from an immunized animal into immortal myeloma cells. Genetic drift, virtually unavoidable over time, thus poses a significant risk to hybridoma-based antibody production. A once useful hybridoma cell line can eventually fail to produce reliable antibody products, limiting the reproducibility of the research depending on them. Underscoring the issue, an impactful 2015 Nature commentary co-signed by over 100 research leaders called for the widespread adoption of recombinant antibody technology to standardize these key reagents and support scientific reproducibility.⁵ Because basic research provides many of the building blocks that drive progress in drug development, making recombinant antibody technology accessible to researchers at every level has been essential to harmonizing research and supporting biomedical innovation.

The accessibility of recombinant antibody technology has not only enabled drug developers to make therapeutic antibody products with greater quality and consistency – it has fueled progress in every phase of drug development, from expediting drug discovery to facilitating the optimization of therapeutic candidates. Because initial drug discovery and development involves identifying and narrowing down a broad range of potential therapeutic candidates based on functionality, manufacturability, and other key traits, the extensive customization and relatively quick production of recombinant antibodies have proven highly advantageous. Cost- and resource-efficient recombinant antibody production enables even small biotech startups to access precisely engineered antibodies for drug discovery. With quick turnaround times, particularly from established suppliers with proprietary cloning techniques, researchers and drug developers can efficiently explore different antibody reconfigurations during discovery and accelerate research progress.

Unlocking the Full Potential of Recombinant Antibody Engineering With Expert Partnerships

Strong partnerships with expert antibody suppliers and contract research and development organizations (CDMOs) are key in helping researchers at every level access both high-quality off-the-shelf options as well as precisely engineered custom antibodies. While some researchers and drug developers may have the sequence of their desired antibody, many lack the expertise necessary to perform complex recombinant antibody engineering. This level of in-depth knowledge is essential to harness the full potential of ADCs, bispecifics, and other formats, enabling fine-tuning of structure and function.

For example, while a bispecific antibody can be engineered in a “traditional” 1:1 Y-shaped format, where each FAb arm binds a separate antigen, 2:1 or 2:2 designs with more binding arms can be suitable to increase antibody avidity. Other factors, such as the function or silencing of an Fc domain, must also be considered in antibody engineering. Specialized expertise can guide researchers in selecting a configuration optimized for their target of interest and desirable pharmacokinetic properties. For complex formats like ADCs and bispecifics, an experienced CDMO can apply precise conjugation techniques, optimize linker chemistries, and ensure high purity in the final product to maximize therapeutic safety and efficacy.

Working with a capable antibody supply partner also ensures access to an efficient and reliable supply of high-quality antibodies from discovery to clinical scale. Most are equipped to produce consistent batches of recombinant antibodies at scale, supporting rigorous testing and regulatory compliance from early development through to commercial production. CDMO partners can provide insight into the manufacturability of candidate antibody therapeutics, ensuring early-stage drug development efforts are funneled into products that will ultimately be viable for commercial-scale production.

A Bright Future for Antibody Therapeutics

Over the past two decades, researchers have made considerable strides in advancing ADCs, bispecific antibodies, and other antibody-based modalities. However, we have only begun to scratch the surface of exploring the possibilities in this field. The advent of recent artificial intelligence (AI)-based tools for antibody discovery has accelerated the process of identifying promising therapeutic candidates, reducing time, cost, and risk for drug developers.⁶

Progress in our understanding of disease etiology, paired with innovative antibody engineering approaches, has also driven progress in developing ADC and bispecific therapeutics for non-cancer indications. In infectious diseases, for example, bispecific antibodies can be leveraged to target multiple viral or bacterial epitopes, enhancing immune system recognition and improving pathogen clearance.⁷ This is particularly valuable in diseases like HIV, hepatitis B, and multi-drug-resistant bacterial infections, where targeting a single antigen has historically limited therapeutic success. Additionally, multispecific antibodies show great potential in treating genetic diseases, as their capacity to target multiple dysfunctional proteins or pathways simultaneously could offer more comprehensive and individualized therapeutic solutions. These innovative applications demonstrate the flexibility of ADCs, bispecifics, and multispecifics, extending their utility beyond cancer and opening new frontiers in precision medicine.

The possibilities for antibody therapeutics are virtually limitless, but these modalities are still far from perfect. Continued efforts to improve efficacy and minimize off-target effects will be necessary to maintain progress. Ongoing efforts to advance linker technology and antibody engineering to create stable, highly specific ADCs, bispecifics, and multispecifics can reduce the risk of systemic toxicity and improve patient outcomes in cancer and beyond. Collaboration can fuel innovation in this space, equipping drug developers and basic researchers alike with the tools and techniques necessary to reach the full potential of this field.

References

1. Bhushan A, Misra P. Economics of Antibody Drug Conjugates (ADCs): Innovation, Investment and Market Dynamics. Current Oncology Reports. 2024;26. doi:https://doi. org/10.1007/s11912-024-01582-x
2. Liu K, Li M, Li Y, et al. A review of the clinical efficacy of FDA-approved antibody-drug conjugates in human cancers. Molecular cancer. 2024;23(1). doi:https://doi.org/10.1186/ s12943-024-01963-7 3.
3. Scott LJ, Kim ES. Emicizumab-kxwh: First Global Approval. Drugs. 2018;78(2):269-274. doi:https://doi.org/10.1007/s40265-018-0861-2 4.
4. Zhao Q. Bispecific Antibodies for Autoimmune and Inflammatory Diseases: Clinical Progress to Date. BioDrugs. 2020;34(2):111-119. doi:https://doi.org/10.1007/s40259- 019-00400-2 5.
5. Bradbury A, Plückthun A. Reproducibility: Standardize antibodies used in research. Nature. 2015;518(7537):27-29. doi:https://doi.org/10.1038/518027a 6.
6. Cheng J, Liang T, Xie XQ, Feng Z, Meng L. A new era of antibody discovery: an in-depth review of AI-driven approaches. Drug Discovery Today. 2024;29(6):103984. doi:https://doi. org/10.1016/j.drudis.2024.103984 7.
7. abozzi G, Amarendra Pegu, Koup RA, Constantinos Petrovas. Bispecific antibodies: Potential immunotherapies for HIV treatment. Methods. 2019;154:118-124. doi:https://doi. Org/10.1016/j.ymeth.2018.10.010

Author Details 

Dr. Catherine Bladen- Vice President, Regional Executive and Principal Advisor, Vector Laboratories

Publication Details 

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