IL 2 Antibody
Description
Definition and Molecular Basis
IL-2 antibodies bind to IL-2, a 15.5–16 kDa cytokine produced primarily by activated CD4⁺ and CD8⁺ T cells . IL-2 regulates lymphocyte proliferation, differentiation, and immune tolerance by interacting with receptors composed of CD25 (α), CD122 (β), and CD132 (γ) subunits . Antibodies against IL-2 fall into two categories:
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Neutralizing antibodies: Block IL-2 binding to its receptors (e.g., JES6-1A12) .
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Complex-forming antibodies: Stabilize IL-2/receptor interactions to bias signaling (e.g., UFKA-20, MAB602) .
Mechanisms of Action
IL-2 antibodies modulate immune responses through distinct mechanisms:
Receptor Selectivity
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CD25 bias: Antibodies like JES6-1D direct IL-2 to high-affinity CD25⁺ T regulatory cells (Tregs), expanding immunosuppressive populations .
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CD122 bias: Antibodies like S4B6 target intermediate-affinity CD122⁺ effector T cells (Teffs) and natural killer (NK) cells, enhancing antitumor activity .
B. Pharmacokinetic Modulation
IL-2/antibody complexes extend cytokine half-life from 2 hours (free IL-2) to >48 hours, reducing dosing frequency .
| Antibody Clone | Target Receptor | Primary Application | Reference |
|---|---|---|---|
| JES6-1A12 | IL-2 neutralization | ELISA, Treg studies | |
| UFKA-20 | CD25 bias | Autoimmunity | |
| MAB602 | CD122 bias | Cancer immunotherapy |
Research Applications
IL-2 antibodies are widely used in:
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ELISA/ELISPOT: Quantify IL-2 secretion (e.g., JES6-1A12 paired with JES6-5H4 for detection) .
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Intracellular staining: Visualize IL-2 production in activated T cells .
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In vivo models: Expand Tregs in collagen-induced arthritis (CIA) or enhance NK cell activity in cancer .
Therapeutic Applications
Autoimmune Diseases
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Low-dose IL-2/antibody complexes (e.g., Aldesleukin) expand Tregs, reducing disease severity in lupus, type 1 diabetes, and rheumatoid arthritis .
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In CIA mice, IL-2/JES6-1D complexes reduced synovial IL-17 and TNF-α by 60% while doubling Treg numbers .
Cancer Immunotherapy
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High-dose IL-2 (HD IL-2) approved for metastatic melanoma and renal cell carcinoma achieves 14–16% response rates but causes severe toxicity .
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Engineered IL-2/antibody fusions (e.g., MAB602-IL-2) improve safety by selectively activating CD8⁺ T cells, showing 30–50% tumor regression in preclinical models .
Clinical Trials and Outcomes
Recent Engineering Advances
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Covalent IL-2/antibody fusions: Single-agent proteins like MAB602-IL-2 stabilize cytokine-antibody interactions, improving Treg selectivity and pharmacokinetics .
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Species cross-reactivity: Humanized antibodies (e.g., AF-202-NA) show activity in primates, aiding translational research .
Challenges and Future Directions
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Toxicity: HD IL-2 causes capillary leak syndrome (CLS) in 30–50% of patients . Next-gen antibodies aim to decouple Teff activation from toxicity.
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Timing dependence: IL-2 efficacy in autoimmunity depends on early administration; late use may exacerbate inflammation .
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Dual targeting: Antibodies like UFKA-20 that block CD122 while preserving CD25 binding could optimize Treg:Teff ratios .
Product Specs
T-cell growth factor (TCGF), Interleukin-2, Lymphokine, IL-2.
Product Science Overview
Interleukin-2 (IL-2) is a cytokine that plays a pivotal role in the regulation of immune responses. It is primarily produced by activated T cells and is essential for the growth, proliferation, and differentiation of various immune cells, including T cells, B cells, natural killer cells, and macrophages. The mouse anti-human IL-2 antibody is a monoclonal antibody that specifically targets human IL-2, making it a valuable tool in immunological research and therapeutic applications.
IL-2 was first discovered in the 1970s as a T cell growth factor. Its discovery marked a significant milestone in immunology, as it provided insights into the mechanisms of T cell proliferation and the regulation of immune responses. IL-2 is crucial for the maintenance of immune tolerance and the prevention of autoimmune diseases. It also plays a role in the activation and expansion of cytotoxic T cells and natural killer cells, which are essential for the body’s defense against infections and cancer.
IL-2 is a glycoprotein composed of 133 amino acids. It exerts its biological effects by binding to the IL-2 receptor (IL-2R), which is expressed on the surface of immune cells. The IL-2R is a heterotrimeric complex consisting of three subunits: IL-2Rα (CD25), IL-2Rβ (CD122), and IL-2Rγ (CD132). The binding of IL-2 to its receptor triggers a cascade of intracellular signaling pathways that promote cell proliferation, survival, and differentiation.
Recombinant human IL-2 (rhIL-2), also known as aldesleukin, has been approved by the Food and Drug Administration for the treatment of metastatic melanoma and renal cell carcinoma. However, its clinical use is limited by its short half-life and the activation of regulatory T cells (Tregs), which can suppress anti-tumor immune responses. To overcome these limitations, researchers have developed modified versions of IL-2 with improved pharmacokinetic properties and selective activation of effector immune cells .
The mouse anti-human IL-2 antibody is a monoclonal antibody that specifically binds to human IL-2. It is produced by immunizing mice with human IL-2 and subsequently isolating and cloning the antibody-producing B cells. This antibody is widely used in research to study the role of IL-2 in immune responses and to develop IL-2-based therapies. It can be used in various applications, including enzyme-linked immunosorbent assays (ELISA), flow cytometry, and neutralization assays.
Recent advancements in IL-2 research have focused on engineering IL-2 variants with enhanced therapeutic efficacy and reduced toxicity. For example, MDNA11 is a long-acting IL-2 superkine that has been engineered to selectively activate anti-cancer immune cells while minimizing the activation of Tregs . This modified IL-2 has shown promising results in preclinical studies, demonstrating potent anti-tumor activity and a favorable safety profile.
