Reduce functional mass of activated T cells using immunosuppressive drugs
SOC in multiple autoimmune diseases. Active research to refine target specificity and reduce toxicities. Combinations of drugs working at different sites of action using subtoxic doses preferred
Anti‐CD20
B‐cell depletion
SOC and off‐label uses
Anti‐BAFF
Initial B‐cell depletion followed by mobilization of memory B cells. Concurrent inhibition of BAFF signaling in T cells
SOC in SLE. Broad future potential, especially in combination regimens
Anti‐BAFF, followed by anti‐CD20
Depletion of memory B cells mobilized by anti‐BAFF
Sequential use to eliminate mobilized memory B cells to increase efficacy
Anti‐CD40
Block CD40–CD40L (CD154) costimulation of T cells and B cells
POC. Clinical trial initiated in transplantation
Block IgG recycling and increase IgG clearance
First in class antibody fragment to block FcRn (efgartigimod)
POC to reduce pathogenic autoantibodies and formation of immunoglobulin–autoantigen complexes
Prevent egress of activated T cells from lymph nodes
Block sphingosine‐1‐phosphate receptors
SOC in MS, new agents in development
MDSCs
Inhibit activation and proliferation of autoreactive T cells
POC in preclinical models. Plans for clinical trials in RA
Decrease proinflammatory cytokines
Anti‐TNF‐α or TNF‐α receptor
Decrease TNF‐α mediated tissue injury and proinflammatory signaling
SOC in multiple autoimmune diseases
Anti‐IL‐6 or anti‐IL‐6R
Decrease pathological consequences of proinflammatory IL‐6 signaling in innate and adaptive immune response
SOC in RA, clinical trials ongoing
Anti‐IL‐12
Decrease pathological consequences of proinflammatory IL‐12 signaling in innate and adaptive immune response
Monoclonal antibody against p40 subunit. SOC in psoriasis and Crohn's disease. Also blocks IL‐23 signaling
Anti‐IL‐23
Decrease pathological consequences of proinflammatory IL‐23
Monoclonal antibody against p40 subunit. SOC in psoriasis and Crohn's disease. Blocks IL‐23 stimulation of Th17 cells
Anti‐IL‐17
Decrease pathological consequences of Th17 production of IL‐17
SOC for psoriasis and psoriatic arthritis. Clinical trials designed
Anti‐IL‐21
Decrease multiple pathological consequences of IL‐21 in innate and adaptive immune responses
Clinical trials in RA, T1DM, Crohn's disease
Inhibition of proinflammatory cytokine signaling
IL‐2
Decrease proliferation of activated CD4 and CD8 T cells
SOC CNI and mTOR inhibitors. POC JAK3 inhibition
IL‐6
Decrease proinflammatory IL‐6R‐mediated signaling
POC and SOC indications for JAK1/2 inhibition
IL‐12/IL‐23
Decrease proinflammatory IL‐12 and IL‐23 signaling that polarize to a Th1 response, increase secretion of IFN‐γ and TNF‐α, increase cytotoxicity of NK cells and CD8 CTLs and drive differentiation of pathogenic Th17 cells
POC and SOC indications for JAK2 inhibition
IFN‐α/IFN‐β
Decrease gene expression induced by type 1 IFNs
POC and SOC indications for JAK1 inhibition
IFN‐γ
Decrease proinflammatory actions of IFN‐γ produced by NK, NKT, CD4 and CD8 T cells
POC and SOC indications for JAK1/JAK2 inhibition
Immunosuppressant cytokines
rHuIL‐10
Antagonize Th1‐mediated pathology
SOC to prevent pancreatitis post‐ERCP. Trial in ulcerative colitis terminated for concern over Guillain–Barré syndrome
Inhibition of transendothelial migration of effector cells
Anti‐chemokine receptors or integrins
Prevent injury by blocking egress of effector cells from blood into target tissues
Block of α4β7 integrin ineffective in PSC. Potential for studies of other FDA‐approved chemokine/integrin inhibitors
Physiologic immunoregulation
PIF
Administration to recreate immunosuppressive and immunomodulatory environment of the fetus and mother during pregnancy
