Table 2.
Potential points of therapeutic intervention to inhibit complement for cancer treatment.
| Intervention point | Drug example | Hypothetical advantages and disadvantages of each intervention point | ||||
|---|---|---|---|---|---|---|
| Pathway-specific Inhibition |
Cl-INH | Advantages: | ||||
| Preserve the beneficial functions of the other initiating pathways | ||||||
| Supported by a genetic models of cervical cancer (C4 KO) | ||||||
| Disadvantages: | ||||||
| More than one pathway may be involved in cancer progression | ||||||
| C3 inhibition | Compstatin | Advantages: | ||||
| Broadest effect | ||||||
| Supported by genetic models of cervical and ovarian cancer (C3 KO) | ||||||
| C5 inhibition | Eculizumab | Advantages: | ||||
| Intact complement deposition at the C3 level | ||||||
| Avoids the sublytic effect of MAC | ||||||
| Disadvantages: | ||||||
| No tested in in vivo cancer models | ||||||
| C5a/C5aR Inhibition |
PMX-53 | Advantages: | ||||
| Experimental data supporting the protumoral activity of C5a | ||||||
| Supported by preclinical models of cervical, ovarian, and lung cancer | ||||||
| Disadvantages: | ||||||
| Only one effector molecule is inhibited, while others may also be important (e.g., C3a) | ||||||