The Anti-IL-15 [ExNK] monoclonal antibody is developed explicitly for in vivo cytokine neutralization in nonhuman primates (NHPs), particularly Macaca mulatta (rhesus macaques). It is an IgG1L isotype with LALA and LS mutations engineered into the Fc region to minimize Fc receptor binding (LALA) while extending serum half-life (LS mutation). These modifications enable effective and sustained neutralization of IL-15 with reduced engagement of Fc-mediated effector functions, making it ideal for prolonged depletion or modulation of NK cell activity in preclinical research settings.
Interleukin-15 (IL-15) plays a pivotal role in developing, surviving, and activating natural killer (NK) cells and memory CD8+ T cells. By neutralizing IL-15, this antibody provides a tool for extended NK cell depletion, allowing investigators to dissect the role of NK cells in immune responses, infection, transplantation, and cancer models.
The [ExNK] construct is based on extending the half-life of a previous version (CAT-00234, RRID:AB_2716329; Described in PMID: 27430715). It has been validated for in vivo applications in rhesus and pigtail monkeys and is supplied without conjugates, ensuring flexibility for diverse experimental designs. Consistently with the previous published version, a single infusion results in a reduction of 80-90% of NK cells (defined as CD3- CD20- CD8alpha+ CD14- NKG2A+ lymphocytes; see data from collaborators Afam Okoye and Ben Varco-Merth, OSHU). Its non-activating Fc modifications make it particularly suited for studies requiring a prolonged reduction in NK cell populations without confounding effects of antibody-dependent cellular cytotoxicity (ADCC).
Applications
In vivo NK cell depletion is designed for extended depletion of NK cells in rhesus macaques via IL-15 neutralization, without triggering cytotoxic Fc-mediated mechanisms.
Cytokine Neutralization Studies : Investigations into IL–15–mediated immune processes in infectious disease models, tumor immunology, and transplantation biology.
Immunomodulation Research is Useful in evaluating the impact of NK cell function and IL-15 signaling on the immune system over prolonged periods.
Performance
Figure. Comparison of the NK reduction efficacy of the half-like extended anti-IL-15 [ExNK] with the previous NHPRR product [M111R1]. (Okoye, Varco-Merth, 2025) All RM were chronically-infected with SIVmac239 and received 3 doses at 10 mg/kg (IV).
Control antibody options
Rhesus IgG1 Kappa, against an irrelevant target - Control antibody rhesus IgG1 (anti-DSP) RRID:AB_2716330
Rhesus IgG1 Lambda, against SARS - Anti-SARS-CoV-2 [2-7L] RRID:AB_3086858
Rhesus IgG4 Kappa with LALA mutations, against SARS Anti-SARS-CoV [S309R4] RRID:AB_2941328
Rhesus IgG1 Kappa with LS mutations, against SIV/HIV Anti-HIV [rh3BNC117LS] RRID:AB_2941336 or Anti-SIV [ITS103.01LS] RRID:AB_2941356
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