Table 1

Comparison between first-, second-, and third-generation ADCs

Properties/GenerationFirst-generation ADCsSecond-generation ADCsThird-generation ADCs
Antibody typeMurine or chimeric antibodiesHuman-mouse chimeric antibodies, humanized monoclonal antibodiesFully human monoclonal antibodies
LinkerUnstableCleavable and non-cleavableMore stable, site-specific
CytotoxinLower toxicityHigher toxicityVarious highly effective small molecule toxins
Drug-to-antibody ratioNon-uniformNon-uniformUniform
TargetingLowerHigherHighest
ImmunogenicityHighLowerLowest
SafetyStronger toxicity/side effectsStronger side effectsLower toxicity
Clinical efficacyPoor effectBetter effectBest effect
Clinical applicationFew clinical applicationsWidespread clinical applicationWidespread application with significant effects
FeaturesNon-site-specific conjugation, short half-lifeSite-specific conjugation, improved efficacySite-specific conjugation, wider therapeutic window

ADCs, antibody-drug conjugates.