Anti-Human IL-6 (Siltuximab) [Clone CNTO-328] — Fc Muted™
Anti-Human IL-6 (Siltuximab) [Clone CNTO-328] — Fc Muted™
Product No.: I-455
Product No.I-455 Clone CNTO-328 Target IL-6 Product Type Biosimilar Recombinant Human Monoclonal Antibody Alternate Names BSF-2, CDF, Hybridoma growth factor (HPGF), IFN-beta-2, HSF Isotype Human IgG1κ Applications B , ELISA , FA , IF , RIA |
Antibody DetailsProduct DetailsReactive Species Human Expression Host HEK-293 Cells FC Effector Activity Muted Product Concentration ≥ 5.0 mg/ml Endotoxin Level < 1.0 EU/mg as determined by the LAL method Purity ≥95% by SDS Page ⋅ ≥95% monomer by analytical SEC Formulation This biosimilar antibody is aseptically packaged and formulated in 0.01 M phosphate buffered saline (150 mM NaCl) PBS pH 7.2 - 7.4 with no carrier protein, potassium, calcium or preservatives added. Due to inherent biochemical properties of antibodies, certain products may be prone to precipitation over time. Precipitation may be removed by aseptic centrifugation and/or filtration. State of Matter Liquid Product Preparation Recombinant biosimilar antibodies are manufactured in an animal free facility using only in vitro protein free cell culture techniques and are purified by a multi-step process including the use of protein A or G to assure extremely low levels of endotoxins, leachable protein A or aggregates. Pathogen Testing To protect mouse colonies from infection by pathogens and to assure that experimental preclinical data is not affected by such pathogens, all of Leinco’s recombinant biosimilar antibodies are tested and guaranteed to be negative for all pathogens in the IDEXX IMPACT I Mouse Profile. Storage and Handling Functional grade preclinical antibodies may be stored sterile as received at 2-8°C for up to one month. For longer term storage, aseptically aliquot in working volumes without diluting and store at ≤ -70°C. Avoid Repeated Freeze Thaw Cycles. Regulatory Status Research Use Only Country of Origin USA Shipping 2 – 8° C Wet Ice Additional Applications Reported In Literature ? FA, ELISA, B, RIA, IF Each investigator should determine their own optimal working dilution for specific applications. See directions on lot specific datasheets, as information may periodically change. DescriptionDescriptionSpecificity This non-therapeutic biosimilar antibody uses the same variable region sequence as the therapeutic antibody Siltuximab. CNTO-328 (Siltuximab) is a neutralizing monoclonal antibody specific against human IL-6. Background IL-6 is a pleiotropic 26 kD protein that can act as both a pro-inflammatory cytokine and an anti-inflammatory myokine, a form of cytokine produced in muscle cells that participates in tissue regeneration and repair, maintenance of healthy bodily functioning, and homeostasis within the immune system 1. IL-6 also plays a part in the endocrine, nervous, and hematopoietic systems, bone metabolism, regulation of blood pressure, and inflammation. Furthermore, IL-6 is an important mediator of fever and of the acute phase response which is the body's rapid attempt to restore homeostasis after tissue injury, infection, neoplastic growth, or immunological disturbance. In its role as an anti-inflammatory myokine, IL-6 precedes the appearance of other cytokines in the circulation, is notably elevated with exercise, and is mediated by both its inhibitory effects on TNF-α and IL-1, and activation of IL-1R⍺ and IL-10. IL-6 signals through a cell-surface type I cytokine receptor complex formed by the binding of IL-6 to IL-6R, which in turn combines with GP130 to transduce extracellular signaling via STAT3 activation. Hence, it is thought that blocking the interaction between IL-6 and GP130 may have therapeutic potential via the inhibition of the IL-6/GP130/STAT3 signaling pathway. Moreover, IL-6 initiates inflammatory and auto-immune processes in many diseases, including diabetes, atherosclerosis, depression, Alzheimer's disease, rheumatoid arthritis, and cancer. For example, multicentric Castleman’s disease is a rare lymphoproliferative disorder caused by dysregulation of IL-6 2. Thus, there is an interest in the therapeutic potential of anti-IL-6 mAbs.
CNTO-328 (Siltuximab) is a chimeric monoclonal antibody that was developed for the treatment of IL-6 related disorders 2,3,4,5. Siltuximab is associated with sustained reductions in IL-6 levels along with various other cytokines and markers 2. In vitro studies in ovarian cancer cells show that siltuximab inhibits IL-6 induced STAT3 activation, nuclear translocation, and downstream gene expression 6. Siltuximab also induces apoptosis 2,7 and reduces C-reactive protein levels 2. Siltuximab has been approved for the treatment of multicentric Castleman’s disease in HIV-negative patients 1. Siltuximab does not bind to virally produced IL-6 (vIL-6). Antigen Distribution IL-6 is a pleiotropic cytokine produced by B lymphocytes, T lymphocytes, macrophages, microglia, fibroblasts, keratinocytes, mesangial cells, vascular endothelial cells, mast cells, and dendritic cells. Additionally, osteoblasts secrete IL-6 to stimulate osteoclast formation. Smooth muscle cells in the tunica media of many blood vessels produce IL-6 as a pro-inflammatory cytokine. IL-6 is also released into circulation in response to various stimuli including PAMPs (pathogen-associated molecular patterns) and cortisol, a hormone produced by the human body under psychologically stressful conditions.
Ligand/Receptor IL6R NCBI Gene Bank ID UniProt.org Research Area Biosimilars . Cell Biology . Immunology . Inflammatory Disease . Innate Immunity . Neuroscience . Autoimmunity . Pro-Inflammatory Cytokines Leinco Antibody AdvisorPowered by AI: AI is experimental and still learning how to provide the best assistance. It may occasionally generate incorrect or incomplete responses. Please do not rely solely on its recommendations when making purchasing decisions or designing experiments. Research-grade Siltuximab biosimilars are typically used as calibration standards or reference controls in a pharmacokinetic (PK) bridging ELISA by serving as the analytical standard for establishing the assay’s standard curve and for quantifying both the biosimilar and reference products in serum samples. Key use and justification:
Summary Table: Use of Siltuximab Biosimilar in PK Bridging ELISA
Important context:
If you need guidance on practical ELISA setup (e.g., plate layout, dilution scheme), that can be provided as well. The primary models in which a research-grade anti-IL-6 antibody is administered in vivo to study tumor growth inhibition and characterize tumor-infiltrating lymphocytes (TILs) are:
Essential context and supporting details:
Recommended usage for TIL characterization:
Examples of common models:
Model selection depends on:
In summary, research into anti-IL-6 therapy and its impact on tumor growth and TILs is conducted primarily using either xenograft models (for direct effects on human tumor cells) or syngeneic models (for studying immune responses and TIL dynamics in a functional immune environment). Researchers use the Siltuximab biosimilar, an anti-IL-6 monoclonal antibody, in combination with other checkpoint inhibitors like anti-CTLA-4 or anti-LAG-3 biosimilars to study synergistic effects in immune-oncology models by targeting distinct but complementary immune pathways. Context and Supporting Details:
Additional Relevant Information:
Summary Table: Combination Rationale and Mechanisms
The synergy is tested experimentally in complex tumor immune models to determine the best combinations for future clinical trials. A Siltuximab biosimilar can be used as both the capture and detection reagent in a bridging ADA ELISA to monitor anti-drug antibodies (ADAs) in patients receiving siltuximab therapy. This method leverages the structural similarity between biosimilar and reference drugs to detect immune responses against the therapeutic. How it works in bridging ADA ELISA:
Key Points:
Limitations:
In summary, a Siltuximab biosimilar in a bridging ADA ELISA acts both as the bait (capture) and the probe (detection), enabling sensitive monitoring of immune responses against the therapeutic drug in patients. References & Citations1. Trikha M, Corringham R, Klein B, et al. Clin Cancer Res. 9(13):4653-4665. 2003. 2. Markham A, Patel T. Drugs. 74(10):1147-1152. 2014. 3. van Zaanen HC, Koopmans RP, Aarden LA, et al. J Clin Invest. 98(6):1441-1448. 1996. 4. van Zaanen HC, Lokhorst HM, Aarden LA, et al. Br J Haematol. 102(3):783-790. 1998. 5. van Zaanen HC, Lokhorst HM, Aarden LA, et al. Leuk Lymphoma. 31(5-6):551-558. 1998. 6. Guo Y, Nemeth J, O'Brien C, et al. Clin Cancer Res. 16(23):5759-5769. 2010. 7. Hunsucker SA, Magarotto V, Kuhn DJ, et al. Br J Haematol. 152(5):579-592. 2011. 8. Voorhees PM, Chen Q, Kuhn DJ, et al. Clin Cancer Res. 13(21):6469-6478. 2007. 9. Cavarretta IT, Neuwirt H, Zaki MH, et al. Adv Exp Med Biol. 617:547-555. 2008. 10. Voorhees PM, Chen Q, Small GW, et al. Br J Haematol. 145(4):481-490. 2009. 11. Karkera J, Steiner H, Li W, et al. Prostate. 71(13):1455-1465. 2011. 12. Kurzrock R, Voorhees PM, Casper C, et al. Clin Cancer Res. 19(13):3659-3670. 2013. 13. van Rhee F, Wong RS, Munshi N, et al. Lancet Oncol. 15(9):966-974. 2014. 14. van Rhee F, Rosenthal A, Kanhai K, et al. Blood Adv. 6(16):4773-4781. 2022. Technical ProtocolsCertificate of Analysis |
Formats Available
Prod No. | Description |
---|---|
I-450 | |
I-455 |
