IL 15 Antibody

Interleukin-15, Mouse Anti-Human
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Description

Functional Roles in Immune Modulation

IL-15 antibodies are used to study or manipulate IL-15-mediated pathways, which include:

  • Immune Cell Activation: IL-15 promotes survival and proliferation of NK cells, CD8+ T cells, and dendritic cells (DCs) . Antibodies blocking IL-15 inhibit these effects, reducing inflammation in autoimmune models .

  • Antibody-Dependent Cellular Cytotoxicity (ADCC): IL-15 enhances ADCC by upregulating Fcγ receptors on NK cells and macrophages. Antibodies against IL-15Rβ (CD122) diminish this activity .

  • Autoimmunity Regulation: Anti-IL-15 antibodies reverse intestinal inflammation in celiac disease models by depleting pathogenic CD8+ T cells .

Key Studies

  • Cancer Immunotherapy: IL-15 antibodies combined with anti-CD20 (rituximab) or anti-CD52 (alemtuzumab) monoclonal antibodies improved tumor clearance in murine models via ADCC .

  • Autoimmune Disease:

    • Vitiligo: Short-term anti-CD122 treatment in mice depleted tissue-resident memory T cells (T<sub>RM</sub>), leading to durable remission .

    • Celiac Disease: Anti-CD122 antibodies reversed villous atrophy in IL-15 transgenic mice, highlighting therapeutic potential .

Mechanistic Insights

  • IL-15 antibodies block signals critical for NK cell survival (e.g., Bcl-2) and cytotoxic function (e.g., perforin, granzyme B) .

  • In dendritic cells, IL-15 inhibition reduces antigen presentation and germinal center B cell responses .

Clinical Applications and Trials

Clinical TrialPhaseTargetOutcome
NCT02689453 (IL-15 + alemtuzumab) IAdult T-cell leukemiaOngoing, with preclinical efficacy in ADCC
Inhaled rhIL-15 in canine metastases IPulmonary metastases39% clinical benefit at MTD (50 µg twice daily)
Subcutaneous rhIL-15 in solid tumors IRefractory cancersExpanded NK/CD8+ T cells; limited toxicity

Challenges and Future Directions

  • Pharmacokinetics: IL-15's short half-life (~2.5 hours) necessitates continuous infusion or engineered formulations (e.g., PEGylation) .

  • Toxicity: High doses cause neutropenia, hypotension, and cytokine release syndrome .

  • Delivery Innovations: Inhaled IL-15 and CAR-T cells expressing membrane-bound IL-15 show promise for localized effects .

Product Specs

Introduction
Interleukin 15 (IL-15) is a cytokine that plays a crucial role in regulating the activation and proliferation of T cells and natural killer (NK) cells, essential components of the immune system. IL-15 shares functional similarities with Interleukin 2 (IL-2), as both cytokines bind to common receptor subunits, potentially leading to competition for receptor binding and mutual regulation of their activities. Notably, the balance between IL-15 and IL-2 has been implicated in controlling the number of CD8+ memory cells, which are vital for long-term immunity. IL-15 exerts its effects by binding to its receptor, triggering the activation of Janus kinase (JAK) family kinases and subsequently leading to the phosphorylation and activation of signal transducer and activator of transcription (STAT) proteins, including STAT3, STAT5, and STAT6. These STAT proteins then translocate to the nucleus and regulate gene expression, influencing immune cell function and survival. Studies in mice suggest that IL-15 may contribute to cell survival by increasing the expression of the anti-apoptotic protein BCL2L1 (BCL-xL), possibly through STAT6-mediated transcriptional activation. Interestingly, IL-15 is transcribed into two alternatively spliced mRNA variants that encode the same protein, highlighting the intricate regulation of its expression.
Formulation
Supplied at a concentration of 1 milligram per milliliter (mg/ml) in phosphate-buffered saline (PBS) after reconstitution.
Shipping Conditions
The antibody is shipped in lyophilized form (freeze-dried) at ambient temperature, allowing for convenient transportation without the need for cold chain logistics.
Storage Procedures
For long-term storage, it is recommended to keep the lyophilized antibody at 4 degrees Celsius in a dry environment to maintain stability. After reconstitution, if the antibody is not intended for immediate use, it is advisable to aliquot and store it at -20 degrees Celsius to preserve its activity and prevent degradation.
Solubility
To reconstitute the lyophilized antibody, sterile water (H2O) should be used. Gently mix the solution to ensure complete dissolution of the antibody powder, ensuring to wash the sides of the vial. Allow 30-60 seconds for the antibody to fully reconstitute before use.
Applications
This IL-15 antibody is suitable for various applications, including direct enzyme-linked immunosorbent assay (ELISA) for detecting and quantifying IL-15 levels, immunoprecipitation for isolating IL-15 from biological samples, and immunohistochemistry for visualizing IL-15 localization in tissues.
Titer
In a direct ELISA setup, a 1:20,000 dilution of this antibody is sufficient to achieve an optical density (O.D.) greater than 1.0. This titer was determined using an alkaline phosphatase-conjugated rabbit anti-mouse immunoglobulin G (IgG) secondary antibody obtained from Jackson Laboratories.
Synonyms
IL-15, MGC9721.
Purification Method
Ion exchange.
Type
Mouse Anti Human Monoclonal.
Clone
YNR-HIL15.
Immunogen
r.Human IL-15.
Ig Subclass
Mouse IgG1.

Product Science Overview

Introduction

Interleukin-15 (IL-15) is a cytokine that plays a crucial role in the immune system by promoting the proliferation and maintenance of natural killer (NK) cells and CD8+ T cells . It is structurally similar to Interleukin-2 (IL-2) and shares some of its functions, but it also has unique properties that make it a valuable target for therapeutic research, particularly in the field of cancer immunotherapy .

Discovery and Structure

IL-15 was discovered in 1994 by two independent research groups . It is a 14-15 kDa glycoprotein encoded by the IL15 gene located on chromosome 4q31 in humans and on chromosome 8 in mice . The gene comprises nine exons and eight introns, with four exons coding for the mature protein . IL-15 is constitutively expressed by a variety of cell types, including monocytes, macrophages, dendritic cells, keratinocytes, fibroblasts, myocytes, and nerve cells .

Function and Mechanism

IL-15 is essential for the development, survival, and function of NK cells and memory CD8+ T cells . It binds to a receptor complex composed of the IL-2/IL-15 receptor beta chain (CD122) and the common gamma chain (CD132), which are shared with IL-2 . This binding triggers signaling pathways that lead to the proliferation and activation of NK cells and CD8+ T cells .

Therapeutic Potential

IL-15 has shown great promise as an immuno-oncology therapeutic due to its ability to enhance the immune response against tumors . However, its clinical application has been limited by its short half-life, which necessitates frequent administration to maintain therapeutic levels . To address this issue, researchers have developed long-acting IL-15 formulations, such as hydrogel microspheres covalently attached to IL-15, which provide sustained release and prolonged immune cell activation .

Mouse Anti-Human IL-15

Mouse anti-human IL-15 antibodies are used in research to study the function and therapeutic potential of IL-15 in human cells. These antibodies can neutralize IL-15 activity, allowing researchers to investigate its role in various biological processes and disease models . They are also used in the development of IL-15-based therapies, as they can help optimize the delivery and efficacy of IL-15 in clinical settings .

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