Recombinant human IL-2
| Product | Unit size | Cat. code | Docs. | Qty. | Price | |
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Recombinant human IL-2 Recombinant cytokine, source: CHO |
Show product |
50 µg 2 x 50 µg 5 x 50 µg |
rcyc-hil2
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Recombinant human interleukin 2 (carrier-free)
InvivoGen offers recombinant human (h) interleukin 2, produced in Chinese hamster ovary (CHO) cells.
Interleukin 2 (IL-2) is a pleiotropic cytokine showing immunostimulatory or immunoinhibitory activity, depending on the target cell [1]. In the 1990s, the recombinant IL-2 Aldesleukin became the first FDA-approved immunotherapeutic drug for the treatment of metastatic renal cell carcinoma and metastatic melanoma [2]. Recombinant IL-2 is often used for ex vivo T cell expansion [1].
Description
InvivoGen's human IL-2 is the naturally occurring wildtype IL-2 cytokine, derived from CHO cells. It can be used to induce its cognate signaling pathway in HEK-Blue™ IL-2 cells (see figure). It has also been successfully tested for T cell activation and propagation. Its size and purity were assessed using SDS PAGE. The predicted size of human IL-2 is ~15 kDa (see figures).
Key features
- Natural wildtype human IL-2
- Tag-free and carrier-free
- Produced in CHO cells
- High-quality: purity ≥ 95% and endotoxin level < 1EU/µg
- Functionally tested
Applications
- Cellular assays
- Cell culture (e.g. T cell expansion, T cell priming, T cell and NK cell differentiation)
- ELISA
Note, that our recombinant human IL-2 does not feature the C125S mutation of aldesleukin (Proleukin®). This mutation, in which serine has replaced the cysteine at position 125, was introduced to stabilize the E. coli-derived cytokine [2]. InvivoGen's hIL-2 is derived from mammalian CHO cells. Production of recombinant proteins in mammalian cells ensures protein glycosylation and bona fide 3D structure. The glycosylation stabilizes proteins against physicochemical instabilities.
References:
1. Pol JG, et al., 2020. Effects of interleukin-2 in immunostimulation and immunosuppression. J Exp Med. 217(1):e20191247.
2. Wrangle JM, et al., 2018. IL-2 and Beyond in Cancer Immunotherapy. J Interferon Cytokine Res.;38(2):45-68.
Figures
Specifications
Source: Chinese hamster ovary (CHO) cells
Alternative name: IL2, Aldeleukin, Proleukin, T cell growth factor, TCGF
Carrier: Carrier-free
Tag: His-tag
UniProt ID: P60568.1
Protein sequence: Ala21-Thr153
Molecular mass: ~ 15 kDa
Solubility: 100 μg/ml in water
Formulation: Lyophilized from a 0.2 μm filtered solution in 20 mM Sodium Phosphate, 150 mM NaCl, and 5% saccharose buffer solution (pH 7)
Quality control:
- Purity: ≥95% (SDS-PAGE)
- Endotoxin Level: ≤ 0.1 EU/μg (measurement by kinetic chromogenic LAL assay)
- The biological activity has been confirmed using HEK-Blue™ IL-2 cells.
Contents
Recombinant human IL-2 is provided lyophilized and is available in three quantities:
- rcyc-hil2: 50 µl
- rcyc-hil2-2: 2 x 50 µl
- rcyc-hil2-5: 5 x 50 µl
Each product is provided with 1.5 ml endotoxin-free water.
Recombinant hIL-2 is shipped at room temperature.
Upon receipt, it should be stored at -20°C.
Avoid repeated freeze-thaw cycles.
Details
Interleukin 2
Interleukin 2 (IL-2) is a pleiotropic cytokine showing immunostimulatory or immunoinhibitory activity, depending on the target cell [1]. It is mainly produced by activated CD4+ T cells in response to antigen stimulation. To a lower extent, it can also be produced by CD8+ T cells and innate immune cells, such as activated dendritic cells (DCs), mast cells, monocytes, and natural killer (NK) cells [1]. IL-2 acts on lymphocytes by binding to the multimeric IL-2 receptor (IL-2R) and thereby engaging several intracellular signaling pathways that modulate lymphocyte survival, proliferation, and function [2].
IL-2 receptor signaling
The IL2R consists of a hetero-complex of up to three subunits: α (IL-2RA), β (IL-2RB), and γ (IL-2RG), also known as CD25, CD122, and CD132, respectively. The γ subunit CD123 is also referred to as the “common” chain (labeled “γc”), as it is shared with the receptors for IL-4, IL-7, IL-9, IL-15, and IL-21 [1]. Due to its high affinity, IL-2 preferentially binds to the trimeric IL-2R, which is mainly expressed on immunosuppressive regulatory T (Treg) cells [1,3]. Interestingly, IL-2 exists in different conformations that favor either trimeric or dimeric IL-2R, resulting in the activation of different immune cells [4].
Upon receptor-ligand binding, the Janus kinase JAK3 phosphorylates JAK1, which in turn recruits SYK (spleen-associated tyrosine kinase). This leads to the phosphorylation and dimerization of the signal transducer and activator of transcription 5A/B (STAT5A/B). After its translocation to the nucleus, it regulates genes encoding immune-related factors such as IL2RA itself, Treg regulator FOXP3, or suppressor of cytokine signaling 1 or 2 (SOCS1/2). IL-2 also activates the Ras/MAPK and PI3K/Akt signaling pathways [1,5].
IL-2 therapeutic targeting
In the 1990s, recombinant IL-2 at high dosage became the first US FDA (Food and Drug Administration) approved immunotherapeutic drug for the treatment of metastatic renal cell carcinoma (RCC) and metastatic melanoma [2]. However, its adverse side effects together with its stimulatory action on immunosuppressive Tregs quickly put the brakes on the initial euphoria [3]. Combinatorial therapy of recombinant IL-2 and immune checkpoint targeting monoclonal antibodies (e.g. anti-CTLA4, PD-1) was reported to overcome these off-target effects and improve response rates [2].
Interestingly, low-dose IL-2 therapy has been shown to ameliorate autoimmune diseases and graft-versus-host disease (GvHD) [4]. Autoimmune diseases, such as rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) are caused by an imbalance between Tregs and Teffs, both of which are activated by IL-2 [6]. Selective antibodies against IL-2 can alter its conformation, thereby resulting in the selective expansion of Tregs or Teffs subsets [4,6].
The IL-2 cytokine, together with IL-7 and IL-15, is currently under investigation for application in ex vivo T cell expansion. These cytokines are used in different concentrations and combinations to improve cell viability, proliferation, and differentiation in CAR T cell culture [8].
Despite its complexity, IL-2-derived therapy remains a promising area of research, with more than 500 clinical trials listed (ClinicalTrials.gov) [7], investigating new and safer IL-2-related reagents in the fight against cancer and autoimmune diseases [2].
References:
1. Pol JG, et al., 2020. Effects of interleukin-2 in immunostimulation and immunosuppression. J Exp Med. 217(1):e20191247.
2. Wrangle JM, et al., 2018. IL-2 and Beyond in Cancer Immunotherapy. J Interferon Cytokine Res.;38(2):45-68.
3. Hernandez R, et al., 2022. Engineering IL-2 for immunotherapy of autoimmunity and cancer. Nat Rev Immunol. (10):614-628.
4. Trotta E, et al., 2018. A human anti-IL-2 antibody that potentiates regulatory T cells by a structure-based mechanism. Nat Med.:1005-1014.
5. Ross SH, Cantrell DA,. 2018. Signaling and Function of Interleukin-2 in T Lymphocytes. Annu Rev Immunol.;36:411-433.
6. Yokoyama Y, et al., 2018. IL-2-Anti-IL-2 Monoclonal Antibody Immune Complexes Inhibit Collagen-Induced Arthritis by Augmenting Regulatory T Cell Functions. J Immunol. ;201(7):1899-1906.
7. Raeber et al., 2022. A systematic review of interleukin-2-based immunotherapies in clinical trials for cancer and autoimmune diseases. medRxiv preprint version.
8. Sudarsanam H, et al., 2022. Influence of Culture Conditions on Ex Vivo Expansion of T Lymphocytes and Their Function for Therapy: Current Insights and Open Questions. Front Bioeng Biotechnol.;10:886637