Interleukin Targeted Therapy

Interleukins are cell-signaling cytokines that are produced by a variety of cells, primarily T cells. Knowledge about their actions has improved the understanding of the pathogenesis of human diseases and provided potential drug targets for targeted therapy.

To date, these research achievements have been translated into clinical use. For example, Mepolizumab (brand name: Nucala) is approved by the U.S. Food and Drug Administration (FDA) in 2015 which is a humanized monoclonal antibody targeted interleukin 5 (IL-5). It's used for the treatment of severe eosinophilic asthma.

Interleukin Targeted Therapy Table

Since interleukins are important for targeted therapy, here we list most of its related drug target, drug name, clinical stage, drug type and manufacturing company.

Drug target Drug name Clinical stage Drug type Company
IL1A, IL1B Rilonacept Approved Human fusion protein Regeneron Pharmaceutical
IL1B Canakinumab Approved Human whole antibody Novartis
IL1R1 Anakinra Approved IL-1 receptor antagonist Amgen, SOBI
IL2RA Daclizumab Approved Humanized whole antibody Roche, Biogen, Abbvie
IL4R Dupilumab Approved Human whole antibody Sanofi, Regeneron Pharmaceutical
IL5 Mepolizumab Approved Humanized whole antibody GlaxoSmithKline
IL5RA Benralizumab Phase III Humanized whole antibody Biowa, MedImmune
IL6 Siltuximab Approved Chimeric whole antibody Janssen
IL6R Tocilizumab Approved Humanized whole antibody Chugai, Genentech
IL9 Enokizumab Phase II Discontinued Humanized whole antibody Genaera, Ludwig Institute for
Cancer Research, MedImmune,
AstraZeneca
IL12B Ustekinumab Approved Human whole antibody Janssen
IL13 Tralokinumab Phase III Human whole antibody MedImmune, AstraZeneca
IL17A Secukinumab Approved Human whole antibody Novartis, Maruho Pharmaceutical
IL17RA Brodalumab Approved Human whole antibody Amegen, AstraZeneca,
Kyowa Hakko Kirin,
Valeant, Leo Pharma
IL22 Fezakinumab Phase II Discontinued Whole antibody Pfizer
IL23A Tildrakizumab BLA Filing Humanized whole antibody Merck Sharp & Dohme,
Sun Pharmaceutical
IL31RA Nemolizumab Phase II Humanized whole antibody Chugai

Interleukin Targeted Therapy In Human Disease

IL1A

Interleukin 1 alpha (IL1A), also known as hematopoietin 1, is a cytokine of the interleukin 1 family which involves in various immune responses, inflammatory processes, and hematopoiesis. Rilonacept, an anti-IL1 targeted therapy, is used for familial chylomicronemia syndrome (FCS), cryopyrin-associated periodic syndromes (CAPS) and muckle-wells syndrome (MWS).

IL1B

Interleukin 1 beta (IL1B), is a member of the interleukin 1 cytokine family which involves in a variety of cellular activities, including cell proliferation, differentiation, and apoptosis. Canakinumab, an anti-IL1B tageted therapy, is used for systemic juvenile idiopathic arthritis, cryopyrin-associated periodic syndromes (CAPS), tumor necrosis factor receptor associated periodic syndrome (TRAPS), hyperimmunoglobulin D syndrome and familial mediterranean fever.

IL1R1

Interleukin 1 receptor type 1 (IL1R1), belongs to the interleukin-1 receptor family which involves in many cytokine-induced immune and inflammatory responses.. It's a receptor for interleukin-1 alpha, interleukin-1 beta, and interleukin-1 receptor antagonist. Anakinra, an anti-IL1R1 targeted therapy, is used for rheumatoid arthritis (RA) and cryopyrin-associated periodic syndromes (CAPS).

IL2RA

Interleukin 2 receptor alpha chain (IL2RA), is a member of the common gamma-chain receptor family. Daclizumab, an anti-IL2RA targeted therapy, is used for rejection of organ transplantation and multiple sclerosis (MS).

IL4R

Interleukin 4 receptor (IL4R), binds interleukin 4 and interleukin 13 to regulate IgE antibody production. It also binds interleukin 4 to promote differentiation of Th2 cells. Dupilumab, an anti-IL4R targeted therapy, is used for atopic dermatitis.

IL5

Interleukin 5 (IL5), is a member of the common beta-chain receptor family which involoves in the regulation of eosinophil formation, maturation, recruitment and survival. Mepolizumab, an anti-IL5 targeted therapy, is used for asthma.

IL5RA

Interleukin 5 receptor alpha chain (IL5RA), also known as CD125, is a member of the common beta-chain receptor family. Benralizumab, an anti-IL5RA targeted therapy, is still under clinical phase III trial which is used for chronic obstructive pulmonary disease (COPD), asthma and hypereosinophilic syndrome (HES).

IL6

Interleukin 6 (IL6), acts as both a pro-inflammatory cytokine and an anti-inflammatory cytokine. Siltuximab, an anti-IL6 targeted therapy, is used for multicentric castleman's disease (MCD).

IL6R

Interleukin 6 receptor (IL6R), also known as CD126, is a subunit of the interleukin 6 (IL6) receptor complex. Tocilizumab, an anti-IL6R targeted therapy, is used for rheumatoid arthritis (RA), juvenile rheumatoid arthritis (JRA) and multicentric castleman's disease (MCD).

IL9

Interleukin 9 (IL9), is a cytokine secreted by CD4+ helper cells that acts as a regulator of a variety of hematopoietic cells. Enokizumab, an anti-IL9 targeted therapy, was designed to treat asthma but failed in clinical phase II trials.

IL12B

Interleukin 12 beta subunit (IL12B), also known as IL12 p40 subunit, is a common subunit of interleukin 12 and interleukin 23. Ustekinumab, an anti-IL12B targeted therapy, is used for plaque psoriasis, active psoriatic arthritis and Crohn's disease.

IL13

Interleukin 13 (IL13), is involved in several stages of B-cell maturation and differentiation. Tralokinumab, an anti-IL13 targeted therapy, is still under clinical phase III trial which is used for asthma, idiopathic pulmonary fibrosis (IPF) and atopic dermatitis.

IL17A

Interleukin 17A (IL17A), is a proinflammatory cytokine produced by activated T cells which can stimulate the expression of IL6 and cyclooxygenase-2 (PTGS2/COX-2), as well as enhance the production of nitric oxide (NO). Secukinumab, an anti-IL17A targeted therapy, is used for psoriasis, psoriatic arthritis and ankylosing spondylitis (AS).

IL17RA

Interleukin 17 receptor A (IL17RA), also known as CDw217, is a member of interleukin 17 (IL-17) family. Brodalumab, an anti-IL17RA targeted therapy, is used for psoriasis vulgaris, psoriatic arthritis, psoriatic erythroderma, pustular psoriasis and plaque psoriasis.

IL22

Interleukin 22 (IL22), is a member of interleukin 10 (IL10) family which binds to a heterodimeric cell surface receptor composed of IL-10R2 and IL-22R1 subunits. Fezakinumab, an anti-IL22 targeted therapy, was designed to treat rheumatoid arthritis (RA)but failed in clinical phase II trials.

IL23A

Interleukin 23 alpha subunit (IL23A), associates with IL12B to form the IL-23 interleukin, a heterodimeric cytokine which functions in innate and adaptive immunity. Tildrakizumab, an anti-IL23A targeted therapy, is under Biologics License Application (BLA) filling. This drug is uesd for treament of plaque psoriasis.

IL31RA

Interleukin-31 receptor A (IL31RA), functions either as a monomer, or as part of a receptor complex with oncostatin M receptor (OSMR). Nemolizumab, an anti-IL23A targeted therapy, is still under clinical phase III trial which is used for atopic dermatitis and pruritus.

the information above was updated by 2017.7