ProPak™ Recombinant Human IL-15 GMP Protein

Catalog #: PPK-015-GMP Datasheet / COA / SDS

Catalog #	Availability	Size / Price	Qty
PPK-015-GMP-010

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Summary Product Datasheets Carrier Free Data Images Reconstitution Calculator Background Related Research Areas

ProPak™ Recombinant Human IL-15 GMP Protein Summary

Closed-System Process In order to de-risk your therapy as much as possible, ProPak GMP cytokines are designed to integrate seamlessly into a closed-system process. The risk of contamination is significantly lowered as a result. Learn more about closed process reagents.
Weldable Tubing Each ProPak bag is outfitted with weldable tubing, so you can connect it directly to your media, then add both to your bioreactor of choice. Tubing is compatible with any bagged media for use in a 1 L bioreactor, such as the G-Rex.
Ready-to-Use Format Supplied in a 3mL frozen liquid format. Extensive quality testing guarantees that the liquid formulation is just as potent and stable as lyophilized equivalents, allowing you to safely take away the need for reconstitution steps.
Reduced Manual Touchpoints By removing both reconstituting and aliquoting steps, there is less hands-on technician time. This drastically reduces risks of error while streamlining your journey to the clinic.

See the ProPak User Manual to learn how to add ProPak GMP cytokines into your closed process.

Product Specifications

Purity

>97%, by SDS-PAGE with quantitative densitometry by Coomassie® Blue Staining. The molecular weight by mass spectrometry is 12761 Da ± 5 Da

Endotoxin Level

<5.0 EU/mL by the LAL method.

Activity

Measured in a cell proliferation assay using MO7e human megakaryocytic leukemic cells. The ED₅₀ for this effect is 0.300-2.60 ng/mL. The specific activity of recombinant human IL-15 is >2.00 x 10⁸ units/mg, which is calibrated against the human IL-15 reference standard (NIBSC code: 95/554).

Source

E. coli-derived human IL-15 protein
Asn49-Ser162
Produced using non-animal reagents in an animal-free laboratory.

Manufactured and tested under cGMP guidelines.

Accession #

P40933.1

N-terminal Sequence
Analysis

Asn49-Trp-Val-Asn-Val-Ile-Ser-Asp-Leu-Lys

Predicted Molecular Mass

13 kDa

SDS-PAGE

9 kDa, under reducing conditions.

Product Datasheets

PPK-015-GMP

Product Datasheet

COA

SDS

Carrier Free

What does CF mean?

CF stands for Carrier Free (CF). We typically add Bovine Serum Albumin (BSA) as a carrier protein to our recombinant proteins. Adding a carrier protein enhances protein stability, increases shelf-life, and allows the recombinant protein to be stored at a more dilute concentration. The carrier free version does not contain BSA.

What formulation is right for me?

In general, we advise purchasing the recombinant protein with BSA for use in cell or tissue culture, or as an ELISA standard. In contrast, the carrier free protein is recommended for applications, in which the presence of BSA could interfere.

PPK-015-GMP

Formulation	Supplied as a 0.2 μm filtered solution in PBS, recombinant HSA, and Trehalose.
Shipping	The product is shipped on dry ice. Upon receipt, store it immediately at the temperature recommended below.
Stability & Storage:	Use a manual defrost freezer and avoid repeated freeze-thaw cycles. A minimum of 6 months when stored between -14 °C and -40 °C. Can be stored up to 2 weeks at 2-8 °C. Refer to lot specific COA for the Use by Date.

Scientific Data

Bioactivity

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ProPak GMP-grade Recombinant Human IL-15 (PPK-015-GMP) stimulates cell proliferation in the MO7e human megakaryocytic leukemic cell line. The ED₅₀ for this effect is 0.300-2.60 ng/mL. Three independent lots were tested for activity and plotted on the same graph to show lot-to-lot consistency of ProPak GMP IL‑15

N/A

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ProPak IL-7 (PPK-007-GMP) and ProPak IL-15 (PPK-015-GMP) were added to Xeno-free Human T cell media in a bag (CCM038-GMP-1B). In parallel, liquid IL-7 (BT-007-GMP-025/LQ) and IL-15 (BT-015-GMP-025/LQ) or lyophilized IL-7 (BT-007-GMP) and IL-15 (BT-015-GMP) were added to Xeno-free Human T cell media in a bottle (CCM038-GMP-1L). After cytokine addition, the concentration of IL-7 (SPCKB-CS-003676) and IL-15 (SPCKB-CS-003688) was determined by the Ella automated immunoassay system. Data is the average of 4 independent experiments with error bars ±SD.

N/A

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ProPak IL-7 (PPK-007-GMP) and ProPak IL-15 (PPK-015-GMP) were compared liquid IL-7 (BT-007-GMP-025/LQ) and IL-15 (BT-015-GMP-025/LQ) or lyophilized IL-7 (BT-007-GMP) and IL-15 (BT-015-GMP). Each were added to Xeno-free Human T cell media in a bag (CCM038-GMP-1B) with 5% huAB Serum. T cells from 3 donors were activated and expanded in G-Rex bioreactors for 9 days and assessed for fold expansion. Data is the average of 4 independent experiments with 3 donors per experiment, error bars ±SD.

Reconstitution Calculator

Background: IL-15

Interleukin 15 (IL-15) is a widely expressed 14 kDa cytokine that is structurally and functionally related to IL-2 and plays an important role in many immunological diseases (1, 2). Mature human IL-15 shares 70% amino acid sequence identity with mouse and rat IL-15. Alternative splicing generates isoforms of IL-15 with either a long or short signal peptide (LSP or SSP), and the SSP isoform is retained intracellularly (3). IL-15 binds with high affinity to IL-15 R alpha (4). It binds with lower affinity to a complex of IL-2 R beta and the common gamma chain ( gamma c) which are also subunits of the IL-2 receptor complex (5). IL-15 associates with IL-15 R alpha in the endoplasmic reticulum, and this complex is expressed on the cell surface (6).

The dominant mechanism of IL-15 action is known as transpresentation in which IL-15 and IL-15 R alpha are coordinately expressed on the surface of one cell and interact with complexes of IL-2 R beta / gamma c on adjacent cells (7). This enables cells to respond to IL-15 even if they do not express IL-15 R alpha (6). In human and mouse, soluble IL-15-binding forms of IL-15 R alpha can be generated by proteolytic shedding and bind up nearly all the IL-15 in circulation (8-10). Soluble IL-15 R alpha functions as an inhibitor that limits IL-15 action (4, 9). Ligation of membrane-associated IL-15/IL-15 R alpha complexes also induces reverse signaling that promotes activation of the IL-15/IL-15 R alpha expressing cells (11). IL-15 induces or enhances the differentiation, maintenance, or activation of multiple T cell subsets including NK, NKT, Th17, Treg, and CD8+ memory cells (12 - 16). An important component of these functions is the ability of IL‑15 to induce dendritic cell differentiation and inflammatory activation (11, 14). IL-15 exhibits anti-tumor activity independent of its actions on NK cells or CD8+ T cells (17). It also inhibits the deposition of lipid in adipocytes, and its circulating levels are decreased in obesity (18).

Immunotherapy treatment with recombinant IL-15 has the advantage of not stimulating Treg cells like IL-2 does but has the drawback of associated toxicity at higher doses. This has led to increased investigation on mitigating IL-15 toxicity and combination immunotherapy approaches using immune checkpoint inhibitors (19, 20). Preclinical and early clinical studies have shown the potential of also using IL-15 in combination with cancer vaccines to improve their anti-tumor response (20).

IL-15 can also be used for the preconditioning of CAR T cells or for engineering cells to express IL-15 in vivo. Adoptive cell transfer of NK cells engineered to express CD19 and IL-15 were well tolerated in patients with CD19-positive cancers (20). IL-15 can be used in combination with other cytokines like IL-21 to increase the efficiency of NK cell expansion and maturation in stem cell culture protocols (21). The combination of IL-15 with IL-7 also promotes expansion of early-differentiated CD8+ T cells in culture with the added benefit of decreasing Treg cell generation, unlike IL-2, for adoptive cell transfer in cancer immunotherapy (22). GMP IL-7 and GMP IL-15 are commonly used in combination for ex vivo expansion of T cells for cellular therapies.

References

De Sabatino, A. et al. (2011) Cytokine Growth Factor Rev. 22:19.
Grabstein, K. et al. (1994) Science 264:965.
Tagaya, Y. et al. (1997) Proc. Natl. Acad. Sci. USA 94:14444.
Giri, J.G. et al. (1995) EMBO J. 14:3654.
Giri, J. et al. (1994) EMBO J. 13:2822.
Dubois, S. et al. (2002) Immunity 17:537.
Castillo, E.F. and K.S. Schluns (2012) Cytokine 59:479.
Budagian, V. et al. (2004) J. Biol. Chem. 279:40368.
Mortier, E. et al. (2004) J. Immunol. 173:1681.
Bergamaschi, C. et al. (2012) Blood 120:e1.
Budagian, V. et al. (2004) J. Biol. Chem. 279:42192.
Mortier, E. et al. (2003) J. Exp. Med. 205:1213.
Gordy, L.E. et al. (2011) J. Immunol. 187:6335.
Harris, K.M. (2011) J. Leukoc. Biol. 90:727.
Xia, J. et al. (2010) Clin. Immunol. 134:130.
Schluns, K.S. et al. (2002) J. Immunol. 168:4827.
Davies, E. et al. (2010) J. Leukoc. Biol. 88:529.
Barra, N.G. et al. (2010) Obesity 18:1601.
Xue, D. et al. (2021) Antib Ther. 4:123.
Wolfarth, A.A. et al. (2022) Immune Netw. 22:e5.
Oberoi, P. et al. (2020) Cells. 9:811.
Chamucero-Millares, J.A. et al. (2021) Cellular Immunol. 360:104257.

Long Name

Interleukin 15

Entrez Gene IDs

3600 (Human); 16168 (Mouse); 25670 (Rat); 102119613 (Cynomolgus Monkey); 493682 (Feline)

Alternate Names

IL15; IL-15; IL-15MGC9721; interleukin 15; interleukin-15

Manufacturing Specifications

GMP Proteins
R&D Systems, a Bio-Techne Brand's GMP proteins are produced according to relevant sections of the following documents: USP Chapter 1043, Ancillary Materials for Cell, Gene and Tissue-Engineered Products and Eu. Ph. 5.2.12, Raw Materials of Biological Origin for the Production of Cell-based and Gene Therapy Medicinal Products.

R&D Systems' quality focus includes:

Designed, manufactured and tested under an ISO 9001:2015 and ISO 13485:2016 certified quality system
Documented and controlled manufacturing process
Control of documentation and process changes by QA
Personnel training programs
Raw material inspection and vendor qualification/monitoring program
Validated equipment, processes and test methods
Equipment calibration and maintenance schedules using a Regulatory Asset Manager
Facility/Utilities maintenance, contamination controls, safety and pest control programs
Material review process for variances
Robust product stability program following relevant ICH guidelines

R&D Systems strives to provide our customers with the analytical characteristics of each product so that customers may determine whether our products are appropriate for their application. Each product is provided with a lot-specific Certificate of Analysis that contains the product's specifications and test results. Quality control testing may include, but is not limited to:

N-terminal amino acid analysis
SDS-PAGE purity analysis
Molecular weight analysis via mass spectrometry
Endotoxin assessment per USP <85> and Ph. Eur. 2.6.14 guidelines
Bioassay analysis
Microbial testing per USP <71> and Ph. Eur. 2.6.1 guidelines
Host cell protein assessment
Host cell DNA assessment
Mycoplasma assessment

Additional testing and documentation requested by the customer can be arranged at an additional cost.

Production records and facilities are available for examination by appropriate personnel on-site at R&D Systems in Minneapolis and St. Paul, Minnesota USA.

R&D Systems sells GMP grade products for preclinical or clinical ex vivo use. They are not for in vivo use. Please read the following End User Terms prior to using this product.

Animal-Free Manufacturing Conditions
Our dedicated controlled-access animal-free laboratories ensure that at no point in production are the products exposed to potential contamination by animal components or byproducts. Every stage of manufacturing is conducted in compliance with R&D Systems' stringent Standard Operating Procedures (SOPs). Production and purification procedures use equipment and media that are confirmed animal-free.

Production