Interleukin 2 Antibody

Interleukin-2, Rat Anti-Mouse
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Description

Definition and Mechanism of Action

Interleukin-2 antibodies are monoclonal antibodies (mAbs) designed to bind IL-2, altering its interaction with IL-2 receptors (IL-2Rs). IL-2 signals via two receptor types:

  • High-affinity trimeric receptors (CD25/CD122/CD132): Expressed constitutively on regulatory T cells (Tregs).

  • Intermediate-affinity dimeric receptors (CD122/CD132): Found on natural killer (NK) cells and memory CD8⁺ T cells .

IL-2 antibodies achieve functional selectivity through two primary strategies:

  1. Immune complex (IC) formation: Antibodies like JES6-1 or S4B6 bind IL-2, sterically blocking specific receptor-binding epitopes. For example:

    • JES6-1 ICs: Bias IL-2 toward CD25⁺ Tregs by obstructing CD122 binding .

    • S4B6 ICs: Favor CD122⁺ effector cells (NK, CD8⁺ T cells) by blocking CD25 interactions .

  2. Fusion proteins: Covalent linkage of IL-2 to an anti-IL-2 mAb (e.g., MAB602) enhances pharmacokinetics and cell-type specificity .

Therapeutic Applications

IL-2 antibodies are investigated for autoimmune diseases, cancer, and transplantation due to their ability to modulate immune tolerance and activation.

Table 1: Key Therapeutic Applications of IL-2 Antibodies

Disease ModelAntibody TypeMechanismClinical OutcomeSource
Rheumatoid ArthritisJES6-1 ICsTreg expansion, IL-17 suppression66.7% ACR20 response (vs. 26.7% placebo)
Systemic LupusIL-2/MAB602 fusionTreg stimulationReduced anti-dsDNA antibodies
Ulcerative ColitisLow-dose IL-2Treg/CD24⁺CD27⁺ B cell expansion53% remission rate
CancerS4B6 ICsNK/CD8⁺ T cell activationTumor growth inhibition (70–90%)

Autoimmunity and Tolerance

  • Low-dose IL-2 (Ld-IL-2): Subcutaneous administration (1–1.5 million IU) in rheumatoid arthritis (RA) increased Tregs by 2.5-fold and achieved 66.7% ACR20 response versus 26.7% with placebo .

  • IL-2/JES6-1 ICs: In collagen-induced arthritis (CIA) models, these complexes reduced synovial inflammation by 60% and doubled Treg suppressive activity .

Cancer Immunotherapy

  • IL-2/S4B6 ICs: Enhanced NK cell cytotoxicity and CD8⁺ T cell proliferation, leading to >80% tumor regression in melanoma models .

  • Single-agent fusion proteins: Covalent IL-2/antibody constructs (e.g., IL-2-MAB602) prolonged serum half-life (>48 hours vs. 2 hours for free IL-2) and reduced pulmonary edema risk .

Table 2: Pharmacokinetic Properties of IL-2 Antibody Constructs

ConstructHalf-LifeTarget Cell SelectivityAdverse Effects
Free IL-22 hoursBroad (Tregs, effectors)Capillary leak syndrome
JES6-1 ICs48 hoursCD25⁺ TregsMinimal toxicity
S4B6 ICs24–36 hoursCD122⁺ effectorsTransient cytopenia
IL-2-MAB602 fusion>72 hoursEffector bias (CD8⁺/NK cells)No weight loss or hepatotoxicity

Future Directions and Challenges

  • Bias engineering: Developing antibodies that allosterically modulate IL-2/receptor interfaces to fine-tune effector vs. Treg responses .

  • Disease-specific formulations: Tailoring ICs for conditions like type 1 diabetes or graft-versus-host disease (GVHD), where Treg deficits drive pathology .

  • Combination therapies: Pairing IL-2 antibodies with checkpoint inhibitors (e.g., anti-PD-1) to overcome tumor resistance .

Product Specs

Introduction
Interleukin 2 (IL-2) is a cytokine crucial for the growth and differentiation of T and B lymphocytes, key components of the immune system. The IL-2 receptor is a complex structure composed of three different protein chains, with the gamma chain also being part of the receptors for interleukins 4 and 7. Interestingly, in mature thymocytes, only one copy of the IL-2 gene is expressed, an unusual regulatory mechanism for precise gene expression control. Studies in mice have shown that disrupting a similar gene leads to an inflammatory bowel condition resembling ulcerative colitis, highlighting the essential role of IL-2 in mounting an effective immune response against foreign substances.
Formulation
The antibody is supplied as a solution with a concentration of 1 milligram per milliliter in phosphate-buffered saline (PBS) after reconstitution.
Shipping Conditions
To maintain stability during transportation, the antibody is freeze-dried and shipped at room temperature.
Storage Procedures
For long-term storage, the lyophilized antibody should be kept at 4 degrees Celsius in a dry environment. Once reconstituted, if not used within a month, it is recommended to divide it into smaller portions and store them at -20 degrees Celsius.
Solubility
To reconstitute the antibody, add sterile water (H₂O) to the vial. Mix the solution gently, ensuring the liquid reaches the sides of the vial, and allow it to sit for 30-60 seconds before use.
Titer
The antibody titer has not been determined using ELISA. However, a 1:1,000 dilution effectively inhibits T cell proliferation stimulated by specific antigens or concanavalin A.
Synonyms

T-cell growth factor (TCGF), Interleukin-2, Lymphokine, IL-2.

Purification Method
Ion exchange.
Type
Rat Anti Mouse Monoclonal.
Clone
NYRmIL-2.
Immunogen
r.Murine IL-2.
Ig Subclass
Rat IgG2a.

Product Science Overview

Introduction

Interleukin-2 (IL-2) is a cytokine that plays a crucial role in the immune response. It is primarily produced by activated CD4+ T cells and is essential for the proliferation and differentiation of T cells. The rat anti-mouse IL-2 antibody is a monoclonal antibody used in research to study the function and regulation of IL-2 in mouse models.

Interleukin-2 (IL-2)

IL-2 is a key regulator of the immune system. It induces cell cycle progression in resting cells and allows for the clonal expansion of activated T cells . IL-2 is also involved in the activation and proliferation of natural killer (NK) cells, which are critical for the body’s defense against infections and tumors .

Rat Anti-Mouse IL-2 Antibody

The rat anti-mouse IL-2 antibody is a monoclonal antibody that specifically binds to mouse IL-2. This antibody is used in various immunological assays to detect and quantify IL-2 levels in mouse samples. It is also used in functional studies to block or neutralize IL-2 activity, allowing researchers to investigate the role of IL-2 in immune responses.

Applications in Research
  1. Immunoassays: The rat anti-mouse IL-2 antibody is commonly used in enzyme-linked immunosorbent assays (ELISA) and flow cytometry to measure IL-2 levels in biological samples.
  2. Functional Studies: By blocking IL-2 activity, researchers can study the effects of IL-2 on T cell proliferation, differentiation, and cytokine production.
  3. In Vivo Studies: The antibody is used in animal models to investigate the role of IL-2 in various diseases, including autoimmune disorders, infections, and cancer.
Significance in Immunotherapy

IL-2 has been explored as a therapeutic agent in cancer immunotherapy due to its ability to stimulate the immune system. However, its clinical use is limited by its short half-life and the activation of regulatory T cells (Tregs), which can suppress the immune response . Researchers are working on engineering IL-2 variants and developing combination therapies to enhance its efficacy and reduce side effects.

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