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Cytokine Targets

https://doi.org/10.1186/s12943-020-01294-3
Cytokines establish a conducive microenvironment for eventual tumor metastasis

Cytokines are a class of small molecule proteins or polypeptides that are stimulated, synthesized or secreted by immune cells (such as monocytes, macrophages, T cells, B cells, NK cells, etc.) and some non-immune cells (endothelial cells, epidermal cells, fibroblasts, etc.). Cytokines can transmit information between cells. Cytokines have immune regulation and effector functions including the regulation of innate immunity, adaptive immunity, hematopoiesis, repair of damaged tissues, cell growth, and differentiation. Cytokines play an important role in the immune system by regulating the intensity and duration of immune responses.

Many cytokines promote or restrict each other in vivo, forming an extremely complex immune regulatory network. Specific cytokines exert their biological effects in autocrine, paracrine or endocrine modes, and have various properties such as pleiotropic, overlapping, antagonistic and synergistic. However, under certain conditions, cytokines can also participate in the occurrence of various diseases, and even trigger cytokine storm and cytokine storm syndrome, resulting in multiple organ damage, functional failure and death. Complex and dynamic interactions between cytokines and their receptors mediate chronic inflammation and immunosuppressive tumor microenvironment (TME) leading tumor progression, metastasis, and reduced response to therapy. Autoimmune diseases are the second largest therapeutic field after tumors. Cytokines are the final effector proteins, blocking their function can effectively relieve tissue damage and inflammation in autoimmune diseases. With the improvement of biopharmaceutical technology, there is a huge growth space for targeted cytokine drugs in the future, which is a promising prospect for the treatment of tumors and autoimmune diseases.

ACROBiosystems is adhering to the philosophy of "Better Biologics for Better Life", and has been deeply involved in the field of recombinant proteins for many years. We have developed a series of recombinant cytokines and their receptor proteins including Interleukins, Growth Factors, Tumor Necrosis Factors (TNFs), Chemokines, Colony-Stimulating Factors (CSFs), Interferons (IFNs), Complement Factors, etc., to meet your drug development needs.

Product Features

Closer to the natural conformation in humans due to expressed by HEK293 cells (Human Embryonic Kidney cells)

Biotinylated cytokines are exclusively produced using Avitag™ site-specific biotinylation technology: the biotinylation only happens on the lysine residue of Avi tag; no interference with the target protein's natural binding activities; the protein orientation is uniform when immobilized on an avidin-coated surface

High purity and homogeneity in structure are verified by both SDS-PAGE and SEC-MALS

High bioactivity of binding with receptor or antibody is verified by ELISA/SPR/BLI/cell-based assay. Protocols shared

Strict quality control to ensure high batch-to-batch consistency (ELISA as QC test)

Various species coverage, suitable for species cross experiments: Human, Mouse, Rat, Cynomolgus, Rhesus Macaque, Rabbit, Canine…

Various labels and tags design

More comprehensive cytokine products, hot cytokine targets are available

Hot Cytokines

IL-2 and IL-2 Receptors Patented Technology IL-4 and IL-4R IL-6 and IL-6R IL-23A&IL-12B IL-15 VEGF TGF-beta FGF TNF-alpha GDF-15 CSF EGF and EGFR IGF-I R IFN Complement C3 Complement C5

Verification Data

High purity and homogeneity in structure verified by SDS-PAGE and SEC-MALS

Human IL-2RB&IL-2RG Heterodimer Protein, Fc Tag&Fc Tag (MALS verified) (Cat. No. ILG-H5254) on SDS-PAGE under reducing condition. The purity of the protein is greater than 95%. As verified by SEC-MALS, the purity is more than 90% and the molecular weight of this protein is around 140-160 kDa.

Biotinylated Human TGFBR2, Fc,Avitag (Cat. No. TG2-H82F6) on SDS-PAGE under reducing condition. The purity of the protein is greater than 95%. As verified by SEC-MALS, the purity is more than 90% and the molecular weight of this protein is around 110-125 kDa.

Biotinylated Human TNF-alpha, His,Avitag (active trimer) (MALS verified) (Cat. No. TNA-H82E3) on SDS-PAGE under reducing condition. The purity of the protein is greater than 95%. As verified by SEC-MALS, the purity is more than 90% and the molecular weight of this protein is around 55-70 kDa.

Human GDF-15, Fc Tag (Cat. No. GD5-H5269) on SDS-PAGE under reducing and non-reducing conditions. The purity of the protein is greater than 95%. As verified by SEC-MALS, the purity is more than 90% and the molecular weight of this protein is around 74-100 kDa.

High bioactivity verified by ELISA (QC tested)

Immobilized Human TGFBR2, Fc Tag (Cat. No. TG2-H5252) at 5 μg/mL (100 μL/well) can bind Biotinylated Human TGF-Beta 1, Avitag (Cat. No. TG1-H8217) with a linear range of 0.1-3 ng/mL (QC tested).

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Immobilized Human M-CSF R, Fc Tag (Cat. No. CSR-H5258) at 2 μg/mL (100 μL/well) can bind Biotinylated Human M-CSF, His,Avitag (Cat. No. MCF-H82E6) with a linear range of 0.1-2 ng/mL (QC tested).

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Immobilized Human 4-1BB, Fc Tag (Cat. No. 41B-H5258) at 0.1 μg/mL (100 μL/well) can bind Biotinylated Human 4-1BB Ligand, Fc, Avitag (Cat. No. 41L-H82F9) with a linear range of 0.4-6 ng/mL (QC tested).

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Immobilized Cetuximab at 2 μg/mL (100 μL/well) can bind Human EGF R, His Tag (Cat. No. EGR-H5222) with a linear range of 0.006-0.025 μg/mL (QC tested).

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Immobilized Human Complement C5, His Tag (Cat. No. CO5-H52Ha) at 2 μg/mL (100 μL/well) can bind Anti-C5a (Human IgG1) with a linear range of 0.2-3 ng/mL (QC tested).

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Affinity verified by SPR/BLI

Erbitux (Cetuximab) captured on CM5 chip via anti-human IgG Fc antibodies surface, can bind Human EGF R, His Tag (Cat. No. EGR-H5222) with an affinity constant of 1.3 nM as determined in a SPR assay (Biacore T200).

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Human IL-2 R beta Protein, His Tag (Cat. No. CD2-H5221) captured on CM5 chip via anti-His antibody, can bind Human IL-15, premium grade (Cat. No. IL5-H4117) with an affinity constant of 21.7 nM as determined in a SPR assay (Biacore T200) (Routinely tested).

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Loaded Anti-IL23A & IL12B MAb (P40 domain) on Protein A Biosensor, can bind Human IL-12B&IL-12A Heterodimer Protein, His Tag&Flag Tag (Cat. No. IL2-H4210) with an affinity constant of 1.07 nM as determined in BLI assay (ForteBio Octet Red96e).

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Loaded Anti-IL23A & IL12B MAb (P40 domain) on Protein A Biosensor, can bind Human IL-23A&IL-12B Heterodimer Protein, His Tag&Tag Free (Cat. No. ILB-H52W5) with an affinity constant of 0.588 nM as determined in BLI assay (ForteBio Octet Red96e).

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High batch-to-batch consistency

Affinity of three different lots of Human IL23A & IL12B, His Tag protein (Cat. No. ILB-H52W5) is verified by binding with Human IL-23R, and the result shows very high batch-to-batch consistency. (BLI)

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Product List

Interleukins and Receptors

Growth Factors and Receptors

VEGFs and Receptors

VEGF110 VEGF120 VEGF121 VEGF164 VEGF165 VEGF189 VEGF-B VEGF-C VEGF-D VEGF R1 VEGF R2 VEGF R3

TGFs and Receptors

TGF-beta 1 Latent TGF-beta 1 LAP (TGF-beta 1) LRRC32 & TGF-beta 1 TGF-beta 2 Latent TGF-beta 2 TGF-beta 3 TGF-beta RII BMP-2 Gremlin

FGFs and Receptors

FGF acidic FGF basic FGF-3 FGF-4 FGF-5 FGF-6 FGF-7 FGF-8E FGF-9 FGF-10 FGF-19 FGF-21 FGF-23 FGF R1 FGF R2 (IIIb) FGF R2 (IIIc) FGF R3 (IIIb) FGF R3 (IIIc) FGF R4

EGFs and Receptors

EGF HBEGF EGFR EGFRVIII

IGFs and Receptors

IGF-I IGF-II IGF-I R IGFBP-3 IGFBP-3 R IGFBP-4 IGFBP-7

GDFs

GDF-15 GFR alpha-like Latent GDF-2 GDF-2 Latent GDF-8

Other Growth Factors and Receptors

CTGF HGF HGF R PDGF-BB PDGF R alpha PDGF R beta

TNFs and Receptors

TNF-alpha TNFR1 TNFR2 TNFSF11 CD40 Ligand CD27 ligand OX40 Ligand CD30 Ligand 4-1BB Ligand TRAIL TRAIL R1 TRAIL R2 TRAIL R4 TWEAK R APRIL BAFF BAFF R LIGHT HVEM GITR GITR Ligand

Chemokines and Receptors

CCL1 CCL2 CCL3 CCL5 CCL7 CCL14 CCL17 CCL19 CCL20 CCL22 CX3CL1 CXCL4 CXCL10 CXCL12/SDF-1 CXCL13 CXCL16 CCR5 CCR8 CXCR4

CSFs and Receptors

M-CSF M-CSF R GM-CSF GM-CSF R alpha G-CSF G-CSF R

IFNs and Receptors

IFN-alpha 1 IFN-alpha 2b IFN-alpha/beta R1 IFN-alpha/beta R2 IFN-gamma IFN-gamma R1

Complement Components

Complement C2 Complement C3 Complement C5 Complement C5a Complement Factor D

Other Cytokines and Receptors

Erythropoietin Betacellulin SCF CD117 MIS RII LIF LIF R Oncostatin M Activin A Activin RIIA NRG1 Beta 1 NRG4 CNTF R alpha

FAQ

How do cytokine pleiotropy and network redundancy affect therapeutic target selection?

A single cytokine can act on several cell types, while different cytokines can produce overlapping biological effects. As a result, blocking one pathway may not fully suppress disease activity, whereas broad inhibition may affect protective immunity or tissue repair. Target selection should therefore consider receptor distribution, disease stage, compensatory pathways, and the desired safety window. Screening related ligands, receptors, and receptor complexes helps distinguish true pathway selectivity from activity that appears specific only in a simplified assay.

How does the expression system affect the structure and biological activity of recombinant cytokines?

The expression system can influence folding, disulfide-bond formation, glycosylation, oligomeric state, and impurity profiles. Mammalian expression is particularly useful for cytokines or receptors that depend on complex extracellular-domain folding or post-translational modification, but it is not automatically required for every cytokine.

Why are purity, molecular homogeneity, and the correct oligomeric state important in cytokine drug discovery?

Some cytokines and cytokine-family proteins function as dimers, trimers, or multi-subunit complexes, so electrophoretic purity alone may not demonstrate a native-like active state. Aggregation, degradation, or incorrect assembly can alter epitope presentation and produce artificial avidity in antibody or receptor-binding assays. SDS-PAGE should therefore be complemented, where relevant, by SEC-MALS, SEC-HPLC, or similar methods and by direct binding or cell-based activity data.

How can site-specifically biotinylated cytokines improve high-throughput binding assays?

Random chemical biotinylation can modify multiple exposed residues and may affect receptor- or antibody-binding regions. AviTag-based site-specific biotinylation places biotin at a defined site, enabling more controlled capture on streptavidin-coated sensors, beads, or plates. This can improve target accessibility and assay consistency, particularly in SPR, BLI, ELISA, and screening workflows. Suitability still depends on tag position, protein format, and the geometry of the specific interaction.

How should assays differ for cytokine-neutralizing antibodies, receptor blockers, and cytokine agonists?

Neutralizing antibodies should be evaluated for inhibition of ligand–receptor binding and downstream function. Receptor blockers may need testing against individual subunits and assembled receptor complexes to define the blocked step. Agonists or engineered cytokines require confirmation of receptor selectivity, signaling strength, and cell-type response. A complete workflow therefore combines molecular binding, competition assays, and mechanism-relevant cellular readouts rather than using one assay format for all therapeutic modalities.

Introduction
Product Features
Hot Cytokines
Verification Data
Product List
FAQ