IL2 Specific Neutra™ Antibody Products

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Interleukin-2 (IL-2) is originally named as T-cell growth factor and is initially identified in the culture supernatant of PHA-stimulated lymphocytes. IL-2 is a 15.5 kDa type 1 four-helix bundle cytokine, which is mainly produced by CD4⁺ T cells after antigen stimulation, and a few by CD8⁺ cells, NK T cells, activated dendritic cells (DCS), and mast cells. IL-2 is one of the most important cytokines in the immune system, which is involved in the regulation of protective immunity and the maintenance of immune tolerance mediated by CD4⁺ regulatory T lymphocytes (Treg). IL-2 as an important immunomodulatory cytokine, as well as a valuable research tool, allows T cell populations to proliferate in vitro assays and immunotherapy regimens.

Fig.1 IL-2 plays multiple roles in shaping the immune response.¹

The IL-2-IL-2R Pathway

The IL-2-IL-2R pathway is important in immunity and is also involved in maintaining self-tolerance. Mice lacking components of the IL-2-IL-2R pathway spontaneously develop severe autoimmune disease. The transcription factors NF-AT, NF-κB, and AP1 are all important in the expression of the IL-2 gene. Signaling mediated by IL-2R essentially occurs via the combination of the IL-2Rβ and the IL-2Rγ chains; while the IL-2Rα chain is only important in rendering a high-affinity receptor. Three signaling pathways can be activated: phosphorylation and dimerization of STAT5, activation of MAPK, and activation of the mammalian target of rapamycin (mTOR).

Fig.2 Signal transduction in the IL-2-IL-2R pathway.²

Development of IL-2 Therapeutics

Conventional cytokine therapy using recombinant proteins has shown clinical efficacy. IL-2 is a T cell growth factor and is approved for the treatment of patients with metastatic melanoma and renal cell carcinoma, with beneficial results in a subset of patients. Investigators have generated IL-2/anti-IL-2 complexes that can preferentially stimulate cytotoxic versus regulatory T cells, as well as mutant variants of IL-2 with higher antitumor efficacy than wild-type IL-2.

Low-Dose IL-2

It is now well established that low-dose IL-2 therapy preferentially activates Treg cells because of the constitutive high expression of IL-2Rα. The first clinical trials to test this method were small-scale proof of concept trials, which showed that low-dose IL-2 can effectively treat hepatitis virus-associated vasculitis and chronic graft-versus-host disease (GVHD).

Antibody-Cytokine Conjugates

Another approach used to alter IL-2 structure is the generation of antibodies to IL-2 that, when complexed with IL-2, can preferentially stimulate expansion of Treg or effector T cells.

Chemical Modifications of IL-2

To improve the therapeutic potential of IL-2, some efforts have been made to engineer or modify IL-2.

Cell Therapy with IL-2

T cells can be genetically engineered to express a mutated version of IL-2Rβ, which will be selectively expanded by a specific mutated IL-2. This raises the prospect of selective expansion of specific T cell populations and can therefore be used to treat autoimmune diseases and cancer.

Creative Biolabs offers nearly ninety different anti-IL2 antibody products. These antibodies are recombinantly expressed and could be used in 16 applications. Customization of IL2-based bispecific antibodies is also available for you here.

REFERENCES

Mitra, Suman, and Warren J. Leonard. "Biology of IL-2 and its therapeutic modulation: Mechanisms and strategies." Journal of leukocyte biology 103.4 (2018): 643-655.
Damoiseaux, Jan. "The IL-2–IL-2 receptor pathway in health and disease: The role of the soluble IL-2 receptor." Clinical Immunology 218 (2020): 108515.

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