Summary of Abs targeting CD80/86 interaction with CD28
| Ab | Properties | Clinical application | Desired effects | Downsides | References |
|---|---|---|---|---|---|
| Abatacept | Fusion protein of the extracellular domain of CTLA-4 is linked to modified Fc portion | FDA-approved for: RA Psoriatic arthritis | Blocks CD80/86 interaction with CD28 Efficacious and relatively safe | Predisposes to infections Costly | [103, 104] |
| Belatacept | Similar to abatacept in structure 4-fold higher affinity to CD86 2-fold higher affinity to CD80 | FDA-approved for: Immunosuppression after renal transplant | Higher graft survival compared to cyclosporine Does not cause nephrotoxicity associated with cyclosporine | Higher early acute rejection | [105, 106] |
| XPro952349 & MEDI5256 | Similar to abatacept in structure Higher avidity to CD80/86 than abatacept and belatacept | - | Decreased humoral response to KLH immunization | - | [107, 108] |
| TAB08 | Agonistic anti-CD28 Ab | Phase 2 clinical trial for RA | At low doses, minimal activation of CD28 preferentially expands Tregs and increases serum IL-10 | Causes cytokine release syndrome if administered with a higher dose | [109–111] |
| FR104 | Pegylated Fab with antagonistic CD28 activity | - | Decreased humoral response to KLH immunization in healthy human volunteers Improved GVHD-free survival in primate models | Increased infectious complications | [112, 113] |
This table shows the various molecules generated to target co-stimulatory molecules (CD80/86) interaction with CD28. Inhibiting this interaction leads to T cell anergy and an inhibited immune response. -: no data. Fab: fragment Ag-binding; GVHD: graft-versus-host disease; TAB08: theralizumab