Table 3 Comparison of different masking strategies of pro-Abs
From: Ab locks for improving the selectivity and safety of antibody drugs
Masking concept | Spatial hindrance-based Ab lock | Affinity peptide-based Ab lock | ||||
|---|---|---|---|---|---|---|
Ab lock | Autologous hinge domain | Coiled-coil (CC) domain | Non-Ab protein fragment (e.g., LAP) | Ab fragment (e.g., dsFv) | Affinity peptide | Mutated antigen |
Schematic |
|
|
|
|
|
|
MW of Ab lock | 3.5 kDa | 5 ~ 9.2 kDa | 40 kDa | 26 kDa | 2.8 ~ 5 kDa | 23.3 kDa |
Masking efficiency (compared with parental Ab) | > 390 fold | 80 ~ 1000 fold | > 1.9 fold | 25 ~ 1000 fold | 8 ~ 48 fold | 8.3 fold |
Immunogenicity | Low | Risk | Low | Risk | Risk | Risk |
Wide applicability | Yes | Yes | Yes | Yes | Customized | Customized |
Ab lock released efficiency (after protease cleaved) | Good | Good | Good | Good | Concerned | Concerned |
Evidence for preventing anti-idiotypic Ab binding | Yes | n.d.a. | n.d.a. | n.d.a. | n.d.a. | n.d.a. |
Evidence for reducing side effect in vivo | Yes | n.d.a. | n.d.a. | Yes | Yes | n.d.a. |
