Table 1

Novel Therapeutic Targets for Immunosuppression

TargetAgent(s)EfficacyRisks/Barriers
Blockade of T-cell costimulation via CTLA-4BelataceptSimilar survival compared to CSA in renal transplant patients
Less renal toxicity
Higher rates of rejection, PTLD, and TB infection
JAK-STAT inhibitionTofacitinibEffective in renal transplant patients compared with TAC and CSA
Less renal toxicity
Higher rates of infection and PTLD
Inhibition of protein kinase CSotrastaurinProlonged graft survival in pre-clinical cardiac studies and renal transplant recipientsHigher rates of rejection compared to CNI regimen
Dose-dependent gastrointestinal toxicity
Inhibition of complement by binding to C5EculizumabReduction in AMR in renal and lung transplant patientsSubstantial cost
IL-6 receptor antagonistTocilizumabReduced allograft rejection and expansion of regulatory T cells in animal models
Reduced alloantibody levels in renal transplant patients
No clinical studies in cardiac transplant recipients
Cleavage of human IgG antibodiesIdeSReduced alloantibody levels in sensitized renal transplant patientsNo clinical studies in cardiac transplant recipients

AMR = antibody-mediated rejection; CNI = calcineurin inhibitor; CSA = cyclosporine; IgG = immunoglobulin G; JAK-STAT = Janus kinase–signal transducer and activator of transcription; IL = interleukin; PTLD = post-transplant lymphoproliferative disorder; TAC = tacrolimus; TB = tuberculosis.