Therapeutic agents and their potential effects on alloantigen presentation in transplantation
| Pathway . | Target . | Commercial examples . | Putative effects . |
|---|---|---|---|
| Targeted therapeutic agents | |||
| DAMP/PAMP inhibition | RAGE inhibitor | PF-04494700 | Inhibit donor DC activation and expansion in the GI tract42 |
| TLR4 inhibitor | Eritoran | Inhibit donor DC activation and expansion in the GI tract42 | |
| Chemokine inhibition | Anti-CCR7 Ab | In development | Prevent migration of alloantigen bearing tissue donor DCs into lymph nodes42 |
| Anti-α4β7 integrin Ab | Vedolizumab | Prevent migration of donor T cells with integrin signatures imprinted by donor DCs42 | |
| Cytokine inhibition | Anti-IL-12/23p40 Ab | Ustekinumab | Inhibit T-cell expansion and Th1/Th17 differentiation in response to APC-derived IL-12/2342 |
| Anti–IL-6 or IL-6 receptor Ab | Siltuximab Tocilizumab | Inhibit T-cell expansion and Th17 differentiation in response to APC-derived IL-642 | |
| Costimulatory molecule inhibition | Antagonistic CD40- Ab | Lucatumumab | Inhibit CD40 and APC activation1 |
| CTLA-4-Fc | Abatacept | Inhibit CD80/86 and APC mediated co-stimulation1 | |
| DC depletion | CD83 Ab | In development | Depletion of activated DCs98 |
| Cell signaling inhibition | Janus kinase inhibitors | Ruxolitinib | Impaired DC activation and migration1 |
| Currently used immune suppressants | Calcineurin inhibition | Cyclosporin tacrolimus | Inhibition of antigen presentation in DCs100 |
| mTOR inhibition | Rapamycin | Promotion of tolerogenic DC phenotype100 | |
| Posttransplant cyclophosphamide | Cyclophosphamide | Depletion of APC? |
| Pathway . | Target . | Commercial examples . | Putative effects . |
|---|---|---|---|
| Targeted therapeutic agents | |||
| DAMP/PAMP inhibition | RAGE inhibitor | PF-04494700 | Inhibit donor DC activation and expansion in the GI tract42 |
| TLR4 inhibitor | Eritoran | Inhibit donor DC activation and expansion in the GI tract42 | |
| Chemokine inhibition | Anti-CCR7 Ab | In development | Prevent migration of alloantigen bearing tissue donor DCs into lymph nodes42 |
| Anti-α4β7 integrin Ab | Vedolizumab | Prevent migration of donor T cells with integrin signatures imprinted by donor DCs42 | |
| Cytokine inhibition | Anti-IL-12/23p40 Ab | Ustekinumab | Inhibit T-cell expansion and Th1/Th17 differentiation in response to APC-derived IL-12/2342 |
| Anti–IL-6 or IL-6 receptor Ab | Siltuximab Tocilizumab | Inhibit T-cell expansion and Th17 differentiation in response to APC-derived IL-642 | |
| Costimulatory molecule inhibition | Antagonistic CD40- Ab | Lucatumumab | Inhibit CD40 and APC activation1 |
| CTLA-4-Fc | Abatacept | Inhibit CD80/86 and APC mediated co-stimulation1 | |
| DC depletion | CD83 Ab | In development | Depletion of activated DCs98 |
| Cell signaling inhibition | Janus kinase inhibitors | Ruxolitinib | Impaired DC activation and migration1 |
| Currently used immune suppressants | Calcineurin inhibition | Cyclosporin tacrolimus | Inhibition of antigen presentation in DCs100 |
| mTOR inhibition | Rapamycin | Promotion of tolerogenic DC phenotype100 | |
| Posttransplant cyclophosphamide | Cyclophosphamide | Depletion of APC? |
Ab, antibody.