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 .
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:
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 .
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 .
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 .
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 .
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 .
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 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 .