Novel formats of antibody conjugates: recent advances in payload diversity, conjugation, and linker chemistry

Tomohiro Fujii, Yutaka Matsuda

In the field of bioconjugates, the focus on antibody - drug conjugates (ADCs) with novel payloads beyond the traditional categories of potent cytotoxic agents is increasing. These innovative ADCs exhibit various molecular formats, ranging from small-molecule payloads, such as immune agonists and proteolytic agents, to macromolecular payloads, such as oligonucleotides and proteins. This review offers an in-depth exploration of unconventional strategies for designing conjugates with novel mechanisms of action and notable examples of approaches that show promising prospects. Representative examples of novel format payloads and their classification, attributes, and appropriate conjugation techniques are discussed in detail. The existing basic technologies used to manufacture ADCs can be directly applied to synthesize novel formatted conjugates. However, a wide variety of new payloads require the creation of customized technologies adapted to the unique characteristics of these payloads. Consequently, fundamental technologies, such as conjugation methods aimed at achieving high drug - antibody ratios and developing stable crosslinkers, are likely to become increasingly important research areas in the future.