Comparison of ADC and recombinant immunotoxin therapeutics
| ADC | Immunotoxin | |
|---|---|---|
| Targeting moiety | Full monoclonal antibody | Antibody fragment |
| Payload | Chemotherapy drug | Bacterial or plant toxin |
| Mechanism of action | Most commonly antitubulin agents | Protein synthesis inhibition |
| Toxicity | Target specific, and most commonly peripheral neuropathy, myelosuppression | Target specific and vascular leak syndrome |
| Approved drugs in class | Trastuzumab 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) |
| Advantages | Demonstrated efficacy in refractory setting | Can kill quiescent and rapidly dividing cells as a single agent |
| Better tolerated than most standard chemotherapy | Ideal 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 effect | No off-target toxicity from bystander effect | |
| Disadvantages | Overlapping mechanism of action to standard chemotherapy | Immunogenicity |
| Cumulative peripheral neuropathy | Target selection more restrictive because payload is effective against many quiescent normal cells |