Unmasking Myths: Decoding ADC Research

About the Paper & Its Authors

Lara Fernandez-Cerezo and colleagues have presented breakthrough insights on Antibody−Drug Conjugate (ADC) research. They debunk myths hampering ADC advancement.



Survey & Methodology: Voices from the Field

With the help of the Accelerated ADC Discovery Searchlight network, 25 experts (holding over 500 years of combined experience) were surveyed. They aimed to identify and debunk prevailing ADC myths.

ADC Component Misconceptions

Payload Myths

Contrary to belief, ADC payloads don’t always need high potency. Respondents disproved this by referencing Enhertu and Trodelvy. Both use less potent topoisomerase 1 inhibitors, showcasing efficacy without the expected high potency.

Linker Myths

Choosing an appropriate linker is vital. Common belief suggests a stable linear linker is essential. Yet, Trodelvy® – with a less stable linker – presents a commendable safety profile. It indicates that extreme linker stability might not always be essential. Furthermore, branch-linked ADCs with multiple PEG conjugations, like OBI-999, have shown promising safety profiles in clinical trials. This challenges the emphasis on linear linkers.

Debunking Myths: Key Insights & Implication

Survey results unveiled 51 ADC myths. Main misconceptions include:

– Rigid adherence to traditional ADC components.
– Overemphasis on manufacturing ease.
– Misunderstandings about the therapeutic window.
– Misconceptions on non-target binding toxicities.
– Overvaluing the bystander effect.
– Miscalculations on translatability.

Addressing these myths can reshape next-generation ADCs, leading to significant advancements.

Conclusion: The Road Ahead

By engaging top ADC professionals, the study unveils myths potentially restraining ADC research. While some myths guided early successes, sticking to them might hinder future progress. Addressing these misconceptions can pave the way for groundbreaking ADC developments.