2.1.1 The success of therapeutic monoclonal antibodies has spurred interest in next-generation versions of the modality. One such innovation in the antibody space is the conjugation of a cytotoxic compound, the payload, to the antibody. The resulting antibody–drug conjugate (ADC) has potential to deliver cytotoxic compounds with the precise specificity of an antibody. Because delivery can be precise at the cellular level, these therapeutics have the potential to greatly reduce the dose required of the cytotoxic compound while also reducing the effects of off-target toxicity.
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2.2.1 Antibody-based therapeutics have enjoyed incredible success in part due to their precise and effective binding capabilities. They can serve as effective flags to highlight tumors and present tumor-associated antigens (TAAs) to the patient’s immune system, but can be limited in their efficacy, however, especially in cases where the immune system is depressed by disease or even the tumor itself.
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2.3.1 The biologic portion of an ADC must be chemically bound to its payload through a linker. These short peptides or small molecules can be attached to the antibody and payload in a variety of chemistries with a range of different effects. It helps to classify them as cleavable or non-cleavable (Table 6 and Figure 13).
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2.4.1 Conjugation technology is, of course, intimately tied to payload and linkers in the ADC. We have summarized some advantages and disadvantages of different technologies in Table 7, and have provided some schematics of different conjugation methods in Figure 14 and Figure 15.
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