ADC Technology Market Share, Global Industry Size, Trends, Technology, and Analysis by 2035
ADC Linker and Conjugation Technologies have emerged as a versatile solution for the development of more efficient and stable antibody drug conjugates.
The global ADC technology market size is estimated to grow from USD 1.18 billion in 2023 to USD 4.37 billion by 2035, representing a CAGR of 11.5% during the forecast period 2023-2035.
Conventional anti-cancer therapeutics are characterized by on-target-off-tumour toxicities, making such therapies detrimental to patients. This limitation led to the development of more efficacious and targeted therapy such as antibody drug conjugates (ADCs). ADCs are a complex and versatile form of anti-cancer therapy, which have been proven to be more effective and less toxic to patients. Such interventions are designed to identify specific antigens that are expressed on the surface of target (cancer) cells so that the effects of the cytotoxin / drug are focused on the elimination of only the tumour cells. Owing to the target specificity component, the approach reduces the chances of damaging normal cells. Over the years, this class of therapeutics has undergone several improvements, most of which were focused on how the highly potent cytotoxic component could be attached to the segment that confers specificity (the antibody). The physical attachment of the aforementioned components is facilitated in a process that is commonly referred to as conjugation, or bioconjugation. This chapter features brief descriptions of the different types of linker and conjugation technologies that are used in the development of ADCs. Further, it offers insights from the industry’s perspective, concerning the future of these technologies.
Antibody Drug Conjugates Antibody drug conjugates (ADCs) are an upcoming class of targeted therapeutic agents. Fundamentally, these complex biotherapeutic entities demonstrate the combination of target specificity of an antibody and therapeutic features of a chemotherapy / cytotoxic drug.
Components of ADCs The failure of first-generation ADCs has been attributed to the use of unstable acid-labile linkers, which are prone to degradation in acidic environment of the cell. Since then, linker technologies have undergone significant advances and improvements. Early linkers, which were derived from the acid cleavable hydrazones, could be cleaved at non target sites and thereby, were known to cause systemic toxicity. To overcome these challenges, second-generation linkers, with improved stability, were developed. Further, third-generation conjugation technologies were developed to generate site-specific ADCs without any engineering / modification of the conjugation site.
It is evident that the evolutionary advances in conjugation and linker technologies have enabled the development of viable treatment options. Such improvements have significantly altered the therapeutic potential and likely applications of ADCs. In other words, succeeding generations of conjugated drugs, based on improved technologies are more selective in targeting diseased cells and have broader therapeutic windows.
Despite the current opinion on the superiority of this class of therapeutics, the existing understanding of the biochemical, immunological, pharmacological, and molecular aspects of ADCs needs to be furthered in order to design and develop better versions of these products. The choice of a suitable target antigen and cytotoxic payload is important, however, the conjugation approach used and linker chemistry involved are equally crucial elements for manufacturing viable leads. In fact, linker instability and product heterogeneity (variations in DAR between conjugate molecules manufactured in a singular batch) are known to severely compromise ADC efficacy and therapeutic window, which may cause difficulties in the lead optimization for clinical application, eventually resulting in trial failure. As a result, there are a number of efforts directed towards the development of better / more stable linkers and site-specific conjugation methods that enable manufacturers to synthesize homogeneous batches of ADCs. The demand for ADCs is on the rise. In this context, it is important to mention that ADCs have also been proven to be more effective in treating bacterial infections than conventional antibiotic-based treatment regimens. Another popular field that has emerged as a potential application area for ADCs, is chronic clinical conditions. In this case, selective payload delivery, using ADCs, to disease-associated biological targets has been demonstrated to reduce side-effects. In terms of novel treatment paradigms, ADCs are also being investigated in combination with small-molecule drugs. The growing popularity of this approach can be attributed to its potential to overcome the concerns related to multi-drug resistance. With the growing demand for ADCs, therapy developers, as indicated earlier, are striving to discover and develop better conjugation methods and the means to further tap into the vast potential of these therapeutics.
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