Table 1.

Comparison of ADC and recombinant immunotoxin therapeutics

ADCImmunotoxin
Targeting moietyFull monoclonal antibodyAntibody fragment
PayloadChemotherapy drugBacterial or plant toxin
Mechanism of actionMost commonly antitubulin agentsProtein synthesis inhibition
ToxicityTarget specific, and most commonly peripheral neuropathy, myelosuppressionTarget specific and vascular leak syndrome
Approved drugs in classTrastuzumab emtansine (for HER-2–positive breast cancer); brentuximab vedotin (for Hodgkin's lymphoma and systemic anaplastic large cell lymphoma)Denileukin diftitox (for cutaneous T-cell lymphoma)
AdvantagesDemonstrated efficacy in refractory settingCan kill quiescent and rapidly dividing cells as a single agent
Better tolerated than most standard chemotherapyIdeal for combination with standard chemotherapy due to nonoverlapping mechanism of action and toxicity profile
Can kill tumor cells that don't express target through bystander effectNo off-target toxicity from bystander effect
DisadvantagesOverlapping mechanism of action to standard chemotherapyImmunogenicity
Cumulative peripheral neuropathyTarget selection more restrictive because payload is effective against many quiescent normal cells