Table 3.
Small-molecule drug effectors
| Effector drug | Ozogamicin | MMAE | Maytansinoid DM1 (mertansine) | Maytansinoid DM4 |
|---|---|---|---|---|
| Origin | Semi-synthetic derivative of γ-calicheamicin (Micromonospora echinospora calichensis–Actinomycete soil bacterium) | Synthetic derivative of dolastatin 10 (Dolabella auricularia–Sea hare) | Synthetic derivative of maytansine (Maytenus serrata–Ethiopian shrub) | Synthetic derivative of maytansine (M serrata–Ethiopian shrub); DM1 with 2 additional methyl groups |
| Class of molecule |
Enediyne-containing antibiotic | Linear cytotoxic pentapeptide | Ansamycin macrolide antibiotic | Ansamycin macrolide antibiotic |
| Mechanism of action |
Intercalates in the minor groove of DNA causing double-stranded breaks | Binds tubulin and inhibits normal microtubule polymerization causing mitotic arrest | Binds tubulin and inhibits normal microtubule polymerization causing mitotic arrest | Binds tubulin and inhibits normal microtubule polymerization causing mitotic arrest |
| Example ADCs (target antigen) | GO (CD33) | BV (CD30) | Ado-trastuzumab emtansine (Her2/neu) | SAR3419 (CD19) |
| INO (CD22) | PV (CD22) | IMGN529 (CD37) | BT062 (CD138) | |
| Polatuzumab vedotin (CD79b) | ||||
| Major toxicities including phase 1 study DLTs |
Thrombocytopenia (DLT); neutropenia (DLT); hepatotoxicity | Thrombocytopenia (DLT); neutropenia (DLT); hyperglycemia (DLT); peripheral neuropathy; pulmonary toxicity | Thrombocytopenia (DLT); hepatotoxicity; interstitial lung disease; peripheral neuropathy |
Ocular/corneal toxicity (DLT); peripheral neuropathy (DLT); neutropenia; thrombocytopenia |
DLT, dose-limiting toxicity.