ADC antibody occasionally induces antigen-mediated anticancer activity. Other challenges for targeting tumor antigens with ADCs include high stromal tumor pressure, physiological and kinetic energy barriers, and bystander effects.
Second-generation ADC is more stable than the first-generation connector, the toxic load is more effective, but based on the random coupling strategy, the conjugation DAR is heterogeneous, the drug stability is low, the non-specific toxicity is increased, and the half-life of the ADCs is reduced. As for the third generation of ADC, owing to site-specific antibody conjugation (sulfur bridge method, introduction of non-natural amino acids, enzymatic strategy), with homogeneous, single ADC is more effective cytotoxic carrier. There are currently four PBD-containing ADCs in Phase I and Phase II clinical trials.
https://www.creative-biolabs.com/adc/antibody-design-and-conjugation.htm