There are several possible off-target effects associated with the ADC's, unstable linker chemistry is one of them. How important is having a stable linker in comparison to making sure that all the components of the ADC are novel. Which would be the first issue to "fix"?
Linker stability, i.e. payload release only at the intended site, IMHO is crucial for the efficacy of any ADC (therapeutic window, side effects).
Esp. the frequently used maleimides have stability issues, but there are more viable options with self-stabilizing features. Controlled release, like self pH dependent self-immolating linker or linker with lysosomal protease sites may be advantageous, too. If you like, take a look at our Linkerology Brochure: https://www.iris-biotech.de/global/linkerology for details.
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