From: Ab locks for improving the selectivity and safety of antibody drugs
Disease | Protease expression (Refs.) | Example of applicable Ab drugs |
---|---|---|
Oncology | ||
Lung cancer | MMP-2 [17], MMP-13 [144], MMP-14 [49], Cathepsin B [76, 163, 184], Cathepsin H [151], Cathepsin S [83], ADAM-8 [68], ADAM-9 [117], ADAM-15 [150], ADAM-17 [117], ADAM-28 [122] | • Nivolumab/Pembrolizumab (anti-PD-1 Ab) • Atezolizumab/Durvalumab (anti-PD-L1 Ab) • Necitumumab (anti-EGFR Ab) • Bevacizumab (anti-VEGF-A Ab) • Ramucirumab (anti-VEGFR2 Ab) |
Colorectal cancer | MMP-2 [49], MMP-7 [26], MMP-9 [52, 197], MMP-13 [189], Cathepsin B [1, 177], Cathepsin L [1, 177], Cathepsin S [57], ADAM-10 [50], ADAM-12 [117], ADAM-17 [12], uPA [159] | • Cetuximab/Panitumumab (anti-EGFR Ab) • Bevacizumab (anti-VEGF-A Ab) • Ramucirumab (anti-VEGFR2 Ab) • Ipilimumab (anti-CTLA-4 Ab) • Nivolumab/Pembrolizumab (anti-PD-1 Ab) |
Breast Cancer | MMP-2 [49, 138], MMP-9 [49, 138], MMP-13 [141], MMP-14 [49], Cathepsin B [46, 48, 62, 84, 120, 158, 174], Cathepsin C [123], Cathepsin L [46, 126, 174], Cathepsin S [153], ADAM-9 [121], ADAM-12 [117], ADAM-15 [86], ADAM-17 [107], ADAM-28 [112], uPA [40, 96, 162] | • Trastuzumab/Trastuzumab emtansine (T-DM1)/Pertuzumab (anti-HER2 Ab) • Atezolizumab (anti-PD-L1 Ab) |
Autoimmune disorders | ||
Rheumatoid arthritis (RA) | • Adalimumab/Infliximab/Golimumab/Certolizumab pegol (anti-TNF-α Ab) • Sarilumab/Tocilizumab (anti-IL-6R Ab) • Rituximab (anti-CD20 Ab) • Secukinumab (anti-IL-17A Ab) | |
Psoriasis | MMP-1 [160], MMP-2 [45, 157, 160], MMP-3 [25], MMP-7 [109], MMP-8 [38], MMP-9 [5, 14, 45, 157, 160], MMP-12 [160, 167], MMP-14 [45], MMP-15 [45], MMP-19 [166], MMP-26 [167], MMP-28 [196], ADAM-10 [109], ADAM-12 [109], ADAM-17 [75], ADAM-33 [3, 198] | • Adalimumab/Infliximab (anti-TNF-α Ab) • Efalizumab (anti-CD11a Ab) • Ustekinumab (anti-IL-12/23 Ab) • Secukinumab/Ixekizumab (anti-IL-17A Ab) • Brodalumab (anti-IL-17R Ab) • Guselkumab/Tildrakizumab/Risankizumab (anti-IL-23 p19 Ab) |
Multiple sclerosis (MS) | MMP-2 [7], MMP-7 [31, 92], MMP-9 [7, 31, 32, 56, 58, 89, 92] | • Natalizumab (anti-α4 integrin Ab) • Alemtuzumab (anti-CD52 Ab) • Ocrelizumab (anti-CD20 Ab) • Daclizumab (anti-CD25 Ab) |
Inflammatory diseases | ||
Chronic obstructed pulmonary disease (COPD) | MMP-1 [139], MMP-7 [155], MMP-8 [139], MMP-9 [139, 142, 155], MMP-12 [139] | • Mepolizumab (anti-IL-5 Ab) • Canakinumab (anti-IL-1β Ab) (Phase 1 clinical trial) |
Inflammatory bowel disease (IBD) | MMP-1 [127], MMP-3 [127], MMP-7 [127, 136], MMP-9 [104, 127], MMP-10 [127], MMP-12 [127], MMP-13 [136] | • Adalimumab/Infliximab/ Golimumab/Certolizumab pegol (anti-TNF-α Ab) • Vedolizumab (anti-α4β7 integrin Ab) • Natalizumab (anti-α4 integrin Ab) • Ustekinumab (anti-IL-12/23 Ab) |
Chronic diseases | ||
Osteoporosis | MMP-1 [10], MMP-2 [10], MMP-9 [10], MMP-13 [10], MMP-14 [10], Cathepsin K [39] | • Denosumab (anti-RANKL Ab) • Romosozumab (anti-Sclerostin Ab) |
Alzheimer’s disease (AD) | BACE1 [190] | • Aducanumab (anti-Aβ Ab) (Phase 3 clinical trial) |