Supplementary Material

Synthetic immunology: modulating the human immune system

Barbara Geering1 and Martin Fussenegger1,2

1Department of Biosystems Science and Engineering, ETH Zurich, Mattenstrasse 26, CH-4058 Basel, Switzerland

2Faculty of Science, University of Basel, Mattenstrasse 26, CH-4058 Basel, Switzerland

Corresponding author: Fussenegger M. ()

Table S1: Biologics targeting the immune response

Target / Name / Family / Mechanism of action / Target Disease / Status
Adressin / PF-00547659 / Human Aba / Blocks lymphocyte migration / CDb, UCc / Phase II
B7 / Abatacept / Chimeric CTLA-4 / Block T cell activation / RAd; CD, UC; lupus nephritis, MSe, type I diabetes / FDA-approved as second-line medication; Phase III (terminated); Phase II
Belatacept / Chimeric CTLA-4 / Kidney transplantation / FDA-approved
BLyS / Belimumab / Human Ab / Induces B cell death / SLEf / FDA-approved
CD2 / Alefacept / Chimeric LFA-3 / Induces T cell death / Psoriasis / FDA-approved, not on the market anymore
CD11α / Efalizumab / Humanized Ab / Blocks lymphocyte activation / Psoriasis / FDA-approved, but withdrawn
CD19/ CD3 / Blinatumomab / BiTE / Induces B cell death / ALLg; Non-Hodgkin Lymphoma / Phase III; Phase II
CD19 / MEDI-551 / Humanized Ab / Induces B cell death / Diffuse large B-cell lymphoma / Phase II
CD20 / Rituximab / Chimeric Ab / Induce B cell death / RA, WGh, microscopic polyangiitis / Phase II/III
Ofatumumab / Human Ab / MS, RA / Phase II
Tositumomab / Mouse Ab / N.A.i
Obinutuzumab / Humanized Ab / N.A.
CD22 / Epratuzumab / Humanized Ab / Induces B cell death / SLE, Sjörgens's syndrome / Phase III
CD30/ CD16A / AFM 13 / TandAb / Induces Reed-Sternberg cell death / Hodgkin Lymphoma / Phase II
CD137 / Urelumab / Human Ab / Activates T cells / Melanoma / Phase II
CTLA-4 / Ipilimumab / Human Ab / Activates T cells / melanoma / FDA-approved
Tremelimumab / Human Ab / Melanoma / Phase II
Eotaxin-1 / Bertilimumab / Human Ab / Blocks eosinophil migration / CD, UC / Phase II
GM-CSF / MT203 / Human Ab / Blocks activation of granulocytes and monocytes / RA / Phase I
GM-CSFRα / Mavrilimumab / Human Ab / Blocks activation of granulocytes and monocytes / RA / Phase II
IFN-α / Sifalimumab / Human Ab / Block immune cell activation / SLE / Phase III
Rontalizumab / Humanized Ab / SLE / Phase II
IFN-R / Anifrolumab / Human Ab / Blocks immune cell activation / SLE / Phase II
IgE / Omalizumab / Humanized Ab / Blocks activation of mast cells and basophils / Allergic asthma, chronic spontaneous urticaria / FDA-approved for patients with inadequate response to inhaled corticosteroids
Quilizumab / Humanized Ab / Induces cell death in IgE-producing plasma cells / Asthma / Phase II
IL-1 / Rilonacept / Chimeric protein / Block immune cell activation / CAPSj / FDA-approved
Canakinumab / Human Ab / CAPS; COPDk, coronary artery disease, gout / FDA-approved; phase I
Anakinra / Recombinant protein / RA / FDA-approved for patients with inadequate response to DMARDs
IL-1R1 / MEDI8968 / Human Ab / Blocks immune cell activation / COPD, Hidradenitis Suppurativa / Phase II
IL-2R / Basiliximab / Chimeric Ab / Blocks T cell activation / Renal transplantation / FDA-approved
Daclizumab / Humized Ab / Renal transplantation; MS / FDA-approved; Phase III
IL-4 / Pascolizumab / Humized Ab / Block Th2 differentiation / Asthma / Phase II
Dupilumab / Human Ab / Atopic dermatitis / Phase II
IL-4R / Altrakincept / Synthetic protein / Asthma / Phase II
Pitrakinra / Recombinant protein / Asthma / Phase III
IL-5 / Mepolizumab / Humanized Ab / Block B cell and eosinophil activation / Churg-Strauss Syndrome, severe asthma; nasal polyposis / Phase III; phase II
Reslizumab / Humanized Ab / eosinophilic asthma, eosinophilic esophagitis / Phase II/III ; Phase III
IL-5R / Benralizumab / Humanized Ab / Asthma; COPD / Phase III; Phase II
IL-6 / Sarilumab / Human Ab / Block immune cell activation / RA / Phase II
IL-6R / ALX-0061 / Nanobody / RA / Phase I/ II
Tocilizumab / Humanized Ab / Giant cell arteritis, juvenile idiopathic arthritis, systemic sclerosis; RA / Phase II; Phase III
Sirukumab / Human Ab / RA / Phase III
IL-9 / MEDI-528 / Humanized Ab / Blocks immune cell activation / Asthma / Phase II
IL-12/ IL-23 / Briakinumab / Human Ab / Block Th1 differentiation / CD, MS; Psoriasis / Phase II; Phase III
Ustekinumab / Human Ab / Psoriasis / FDA-approved in patients with inadequate response to conventional therapies
IL-13 / Tralokinumab / Human Ab / Block IgE secretion / Asthma, idiopathic pulmonary fibrosis, UC / Phase II
Anrukinzumab / Humanized Ab / Asthma, UC / Phase II
Lebrikizumab / Humized Ab / Idiopathic pulmonary fibrosis; severe asthma / Phase II; Phase III
IL-17 / Brodalumab / Human Ab / Block cytokine production / Psoriasis, psoriatic arthritis; asthma / Phase III; phase II
Secukinumab / Human Ab / Asthma, Psoriasis / Phase II; Phase III
IL-23 / AMG 139 / Human Ab / Blocks Th17 differentiation / CD / Phase II
Integrin α4/ β7 / AMG 181 / Human Ab / Block lymphocyte migration / CD, UC / Phase II
Natalizumab / Humanized IgG4 Ab / MS, CD / FDA-approved in patients with highly active disease progression and inadequate response to conventional therapies
Vedolizumab / Humanized Ab / CD, UC / Phase III
Integrin β7 / Etrolizumab / Humanized Ab / UC / Phase II
PD-1 / Nivolumab / Human Ab / Block T cell apoptosis mediated by tumor cells / Melanoma, non small cell lung cancer, renal cell carcinoma / Phase III
Pembrolizumab / Human Ab / Melanoma / FDA-approved
TNF / Etanercept / Chimeric protein / Block immune cell activation / ASl, juvenile arthritis, psoriasis, psoriatic arthritis, RA / FDA-approved in patients with inadequate response to DMARDs
Infliximab / Chimeric Ab / AS, CD, Psoriasis, psoriatic arthritis, RA, UC / FDA-approved in patients with inadequate response to conventional therapeutics
Adalimumab / Human Ab / AS, CD, juvenile idiopathic arthritis, psoriatic arthritis, psoriasis, RA, UC / FDA-approved in patients with inadequate response to DMARDS or other conventional therapies
Ozoralizumab / Nanobody / RA / Phase II
Certolizumab pegol / Pegylated Fab of humanized Ab / CD, RA / FDA-approved in patients with inadequate response to conventional therapies
Golimumab / Human Ab / AS, psoriatic arthritis, RA, UC / FDA-approved
COVA322 / FynomAb / Psoriasis, RA / Phase II

aAb, antibody; bCD, Crohn's disease; cUC, ulcerative colitis; dRA, Rheumatoid Arthritis; eMS, multiple sclerosis; fSLE, systemic lupus erythematodes; gALL, acute lymphoblastic leukaemia; hWG, Wegener Granulomatosis; iN.A., not applicable; jCAPS, cryopyrin-associated periodic syndrome; kCOPD, chronic obstructive pulmonary disease; lAS, ankylosing spondylitis