ProPak™ Recombinant Human IL-15 GMP Protein, CF GMP
R&D Systems, part of Bio-Techne | Catalog # PPK-015-GMP
Key Product Details
- 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.
- 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 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.
Product Specifications
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.
Asn49-Ser162
Produced using non-animal reagents in an animal-free laboratory.Manufactured and tested under cGMP guidelines.
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.
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.
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).
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).
Host Cell Protein
<1.00 ng per μg of protein when tested by ELISA.
Mycoplasma
Negative when tested in a ribosomal RNA hybridization assay.
Host Cell DNA
<0.0100 ng per µg of protein when tested by PCR.
Scientific Data Images for ProPak™ Recombinant Human IL-15 GMP Protein, CF
Lot to Lot Consistency
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
ProPak cytokines are successfully recovered into 1L media bags
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.
ProPak cytokines support T cell growth
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.Formulation, Preparation and Storage
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. |
Background: IL-15
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/ gammac 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
Alternate Names
IL15
Entrez Gene IDs
Gene Symbol
IL15
UniProt
Additional IL-15 Products
Product Documents for ProPak™ Recombinant Human IL-15 GMP Protein, CF
Manufacturing Specifications
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:
- Manufactured and tested under an ISO 9001:2015 and ISO 13485:2016 certified quality system
- Documented processes and QA control of documentation and process changes
- Personnel training programs
- Raw material testing and vendor qualification/monitoring
- Fully validated equipment, processes and test methods
- Equipment calibration schedules using a computerized calibration program
- Facility maintenance, safety programs and pest control
- Material review process for variances
- Monitoring of stability over product shelf-life
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 research. The Certificate of Analysis provided contains the following lot specific information:
- N-terminal amino acid analysis, SDS-PAGE analysis, Mass Spectrometry, Host Cell Protein, Host Cell DNA, Mycoplasma testing performed on each bulk QC lot, not on individual finished product lots
- Finished product testing includes bioassay (compliance with an established range), endotoxin level (as determined by LAL assay), and microbial testing according to USP <71>
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.
R&D Systems sells GMP grade products for preclinical or clinical ex vivo cell therapy applications. 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
- All molecular biology procedures use animal-free media and dedicated labware.
- Dedicated fermentors are utilized in committed animal-free areas.
- Protein purification columns are animal-free.
- Bulk proteins are filtered using animal-free filters.
- Purified proteins are stored in animal-free containers in a dedicated cold storage room.
Quality Assurance
- Low Endotoxin Level.
- No impairment of biological activity.
- High quality product obtained under stringent conditions.
Product Specific Notices for ProPak™ Recombinant Human IL-15 GMP Protein, CF
END USER TERMS OF USE OF PRODUCT
The following terms are offered to you upon your acceptance of these End User Terms of Use of Product. By using this product, you indicate your acknowledgment and agreement to these End User Terms of Use of Product. If you do not agree to be bound by and comply with all of the provisions of these End User Terms of Use of Product, you should contact your supplier of the product and make arrangements to return the product.
We suggest you print and retain a copy of these End User Terms of Use of Product for your records.
The End User is aware that R&D Systems, Inc. sells GMP products for preclinical or clinical ex vivo use and not for in vivo use. The End User further agrees, as a condition of the sale of R&D Systems' GMP products that: a) the End User will not use this GMP Product in any procedure wherein the product may be directly or indirectly administered to humans, unless the End User has obtained, or prior to their use will have obtained, an Investigational New Drug (IND) exemption from the FDA and will use the product only in accordance with the protocols of such IND and of the Institutional Review Board overseeing the proposed research, or b) the End User will use the products outside of the United States in accordance with the protocols of research approved by the Institutional Review Board or authorized ethics committee and regulatory agencies to which the End User is subject to in their territory.
R&D Systems, Inc. has the right, at its sole discretion, to modify, add or remove any terms or conditions of these End User Terms of Use without notice or liability to you. Any changes to these End User Terms of Use are effective immediately following the printing of such changes on this product insert. The most recent version of these End User Terms of Use of Product may be found at: RnDSystems.com/Legal.
You agree to review these End User Terms of Use of Product to ensure any subsequent use by you of R&D Systems' GMP Products following changes to these End User Terms of Use of Product constitutes your acceptance of all such changes.
TERMS AND CONDITIONS
The following limitation applies to R&D Systems' warranty and liability for damages: All products are warranted to meet R&D Systems' published specifications when used under normal laboratory conditions.
R&D SYSTEMS DOES NOT MAKE ANY OTHER WARRANTY OR REPRESENTATION WHATSOEVER, WHETHER EXPRESS OR IMPLIED, WITH RESPECT TO ITS PRODUCTS. IN PARTICULAR, R&D SYSTEMS DOES NOT MAKE ANY WARRANTY OF SUITABILITY, NONINFRINGEMENT, MERCHANTABILITY OR FITNESS FOR ANY PARTICULAR PURPOSE.
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For preclinical, or clinical ex vivo use
Not for in vivo use
For preclinical, or clinical ex vivo use
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