IL-15R alpha & IL-15 Fusion Protein, Human (HEK293, Fc)

IL-15R alpha is a high affinity receptor for IL-15 (K_d: 100 pM). IL-15 is essential for the development and function natural killer (NK) cell, NKT cell and memory (m) CD8+ T cell^[1]. IL-15R alpha maintains memory CD8+ T cell homeostasis and lymphocyte development. IL-15R alpha/IL-15 complex can activate the antitumor functions of NK cells and CD8+ T cells^[2][3]. IL-15R alpha & IL-15 Fusion Protein, Human (HEK293, Fc) is a recombinant human IL-15R alpha (I31-D96) & IL-15 (N49-S162) fusion protein with a C-Terminal hFc tag, which is produced in HEK293 cells.

IL-15R alpha is expressed on various cell types, including lymphocytes, myeloid cells, nonlymphoid and nonhematopoietic cells^[4]. IL-15 is produced in macrophages and dendritic cells^[1].
IL-15R alpha is required for transporting of IL-15 from the endoplasmic reticulum to the cell surface to bind with β (CD122) and γ (CD132) chains on responding lymphocytes^[4][5]. When binding with IL-15, the complex increases the in vivo half-life of IL-15 and enhances binding affinity of IL-15 with IL-15Rβ/γ in NK cells and CD8+ T cells. Thus, the signal transmission improves proliferation and antitumor activities of NK cells and CD8+ T cells^[2].
IL-15R alpha forms complex with IL-15 and activates the antitumor functions of NK cells and CD8+ T cells. IL-15R alpha/IL-15 complex is a potential immunotherapeutic agent for cancer and viral infection^[1].

IL-15R alpha (mouse, pre-complexed with hIL-15, i.p., 15 μg, 200 μL) significantly reduces the tumor volume, and induces an early increase of activated NK cells in B16-F10 melanoma mice^[6].
IL-15R alpha & IL-15 Fusion Protein (mouse, i.p., 15 μg & 2.5 μg, 200 μL) causes naive CD8 T cell activation and development into effector cells and long-term memory T cells^[7].

1.The cell proliferation assay using CTLL-2 mouse cytotoxic T cells has an ED₅₀ value of 5-20 ng/mL.
2. Measured by its ability to block human IL-15-induced proliferation of CTLL-2 mouse cytotoxic T cells. The ED₅₀ this effect is 0.2169 ng/mL in the presence of 0.5 ng/mL recombinant human IL-15, corresponding to a specific activity is 4.61×10⁶ units/mg.
3. Measured in a cell proliferation assay using NK92 cells. The EDED₅₀ for this effect is ≤0.3515 ng/mL, corresponding to a specific activity is ≥2.845×10⁶ units/mg.

• 
  Measured by its ability to block human IL-15-induced proliferation of CTLL-2 mouse cytotoxic T cells. The ED₅₀ for this effect is 0.2169 ng/mL in the presence of 0.5 ng/mL recombinant human IL-15, corresponding to a specific activity is 4.61×10⁶ units/mg.

Human

HEK293

C-hFc

Q13261-1 (I31-D96)&P40933-1 (N49-S162, N120D)

3601  [NCBI]&3600  [NCBI]

ITCPPPMSVEHADIWVKSYSLYSRERYICNSGFKRKAGTSSLTECVLNKATNVAHWTTPSLKCIRD&NWVNVISDLKKIEDLIQSMHIDATLYTESDVHPSCKVTAMKCFLLELQVISLESGDASIHDTVENLIILANDSLSSNGNVTESGCKECEELEEKNIKEFLQSFVHIVQMFINTS

Approximately 50-75 kDa due to the glycosylation.

• 
  Greater than 95% as determined by reducing SDS-PAGE.

Lyophilized powder

Lyophilized from a 0.2 μm filtered solution of 20 mM PB, 8% Trehalose, 4% Mannitol, 0.02% Tween80 (w/v), pH 7.5. or 20 mM PB, 150 mM NaCl, pH 7.4 or 20 mM PB, pH 7.4, 8% trehalose, 8% mannitol and 0.02% Tween80.

<1 EU/μg, determined by LAL method.

It is not recommended to reconstitute to a concentration less than 100 μg/mL in ddH₂O.

Stored at -20°C for 2 years. After reconstitution, it is stable at 4°C for 1 week or -20°C for longer (with carrier protein). It is recommended to freeze aliquots at -20°C or -80°C for extended storage.

Room temperature in continental US; may vary elsewhere.

• [1]. Yin Guo, et al. Immunobiology of the IL-15/IL-15Rα complex as an antitumor and antiviral agent. Cytokine Growth Factor Rev. 2017 Dec;38:10-21.  [Content Brief]

  [2]. Johan Mj Van den Bergh, et al. IL-15 receptor alpha as the magic wand to boost the success of IL-15 antitumor therapies: The upswing of IL-15 transpresentation. Pharmacol Ther. 2017 Feb;170:73-79.  [Content Brief]

  [3]. Spencer W Stonier, et al. Trans-presentation: a novel mechanism regulating IL-15 delivery and responses. Immunol Lett. 2010 Jan 4;127(2):85-92.  [Content Brief]

  [4]. Patrick R Burkett, et al. IL-15R alpha expression on CD8+ T cells is dispensable for T cell memory. Proc Natl Acad Sci U S A. 2003 Apr 15;100(8):4724-9.  [Content Brief]

  [5]. Emanuela Romano, et al. Human Langerhans cells use an IL-15R-α/IL-15/pSTAT5-dependent mechanism to break T-cell tolerance against the self-differentiation tumor antigen WT1. Blood. 2012 May 31;119(22):5182-90.  [Content Brief]

  [6]. Isvoranu G, et al. Immunotherapy in cancer-in vivo study of the anti-tumor activity of the IL-15/IL-15R alfa combination in an experimental model of melanoma[J]. Farmacia, 2015, 63: 631-636.

  [7]. Thomas A. Stoklasek, et al. Combined IL-15/IL-15Rα Immunotherapy Maximizes IL-15 Activity In Vivo. J Immunol November 1, 2006, 177 (9) 6072-6080;