Anti-Human RANKL (Denosumab)
Anti-Human RANKL (Denosumab)
Product No.: LT2800
| Product No.LT2800  Clone AMG-162 Target		 RANKL  Product Type  Biosimilar Recombinant Human Monoclonal Antibody  Alternate Names  osteoprotegerin ligand (OPGL), osteoclast differentiation factor (ODF), TNF related activation-induced cytokine (TRANCE), tumor necrosis factor ligand superfamily member 11 (TNFSF11) Isotype		 Human IgG2κ Applications		 ELISA ,  FA ,  IHC ,  WB | 
| Antibody DetailsProduct DetailsReactive Species		 Human Host Species		 Human Expression Host		 HEK-293 Cells FC Effector Activity		 Active Recommended Isotype Controls Immunogen Purified Recombinant Human RANKL 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. 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 (RUO). Non-Therapeutic. Country of Origin		 USA Shipping 2-8°C Wet Ice Additional Applications Reported In Literature ? ELISA, WB, IHC, FA 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 Denosumab. This product is for research use only. Denosumab activity is directed against human RANKL (receptor activator of NFκB ligand). Background Osteoporosis is a disease of bone microarchitecture deterioration commonly seen in postmenopausal women1. Estrogen deficiency leads to low bone mass and increased bone fragility due to bone resorption increasing more than formation. Those affected have an increased risk of fracture. RANKL (receptor activator of NFκB ligand) is a TNF family member that acts as a key bone resorption protein by mediating osteoclast formation, activation, and survival via activating its receptor RANK1,2. 
 Denosumab, a fully human monoclonal antibody originally generated using transgenic Xenomouse technology, selectively and with high affinity binds to and inhibits human RANKL, thus preventing interaction with and activation of its receptor RANK on the surface of osteoclasts and their precursors2. This blocking activity inhibits the formation, function, and survival of osteoclasts, resulting in reduced bone resorption and consequently reduces the risk of vertebral, nonvertebral and hip fractures. Denosumab increases bone mineral density (BMD) and trabecular and cortical bone strength, with continued antifracture and BMD benefits over 10 years of therapy. Bone resorption is inhibited in cynomolgus monkeys and humans, but not normal mice or rats. Unlike bisphosphonates, denosumab is not incorporated into bone and its effects on bone turnover markers, BMD and histomorphometric measures are generally reversed upon its discontinuation1. Antigen Distribution RANKL binds to its receptor RANK, which is located on osteoclasts and osteoclast precursors.  Ligand/Receptor RANK/RANKL NCBI Gene Bank ID UniProt.org Research Area		 Biosimilars . Immunology . Osteoporosis 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 Denosumab biosimilars are used as calibration standards or reference controls in pharmacokinetic (PK) bridging ELISAs to measure drug concentrations in serum samples by employing a standardized and validated protocol. Here's a detailed explanation of how this is typically done: Principle of PK Bridging ELISA
 Reagents and Assay Setup
 Assay Performance
 Validation Considerations
 By using research-grade Denosumab biosimilars as calibration standards in PK bridging ELISAs, researchers can ensure accurate and reliable measurement of Denosumab concentrations in serum samples, which is crucial for pharmacokinetic studies and biosimilar development. Primary Syngeneic and Humanized Models for Anti-RANKL Antibody StudiesThe main research models in which anti-RANKL antibodies have been administered in vivo to study tumor growth inhibition and to characterize tumor-infiltrating lymphocytes (TILs) are syngeneic murine tumor models, particularly in the context of breast cancer. Syngeneic Mouse ModelsKey Models Used: Experimental Approach: Relevance of Syngeneic Models: Humanized Mouse ModelsCurrent Evidence: Combination and Mechanistic StudiesCombination Therapies: Summary Table: Primary Models for Anti-RANKL Antibody Studies
 ConclusionSyngeneic mouse models—especially 4T1, 67NR, and E0771 orthotopic TNBC models—are the primary platforms where research-grade anti-RANKL antibodies have been administered in vivo to study tumor growth inhibition and to characterize resulting TILs. These models enable detailed analysis of immune cell infiltration, activation, and functional changes in response to RANKL blockade, underscoring the importance of the adaptive immune system in mediating anti-tumor effects. Humanized models are not highlighted in the current literature for this specific application. Combination strategies, particularly with chemotherapy, further enhance the immunotherapeutic potential of anti-RANKL in these syngeneic systems. Researchers investigate synergistic effects between the denosumab biosimilar and immune checkpoint inhibitors (ICIs)—including anti-CTLA-4 and potentially anti-LAG-3 biosimilars—by co-administering these agents in preclinical models and clinical studies, especially for cancer patients with bone metastases. The core methodology involves: 
 For checkpoint inhibitors outside anti-PD-1 and anti-CTLA-4 (such as anti-LAG-3 biosimilars), direct published clinical synergy with denosumab biosimilars is not explicitly documented in these results, but similar principles would theoretically apply, and preclinical research may be ongoing. Key insights: 
 In summary, researchers use denosumab biosimilars with ICIs by administering each agent in controlled sequence and combination trials, measuring immune and cancer outcomes, and exploring mechanistic interactions, particularly the modulation of RANK/RANKL signaling and antitumor immunity. A Denosumab biosimilar can be used as both the capture and detection reagent in a bridging ADA ELISA to monitor a patient’s immune response (i.e., development of anti-drug antibodies, or ADAs) against the therapeutic drug. In the bridging ADA ELISA format: 
 Typical workflow: 
 Rationale for using the biosimilar in this way: 
 Additional Notes: 
 Summary Table: Use of Denosumab Biosimilar in Bridging ADA ELISA 
 This method is widely recommended for biosimilar ADA assays to ensure accurate and equivalent detection of immune responses to both biosimilar and originator drugs. References & Citations1. Deeks ED. Drugs Aging. 35(2):163-173. 2018. 2. Kostenuik PJ, Nguyen HQ, McCabe J, et al. J Bone Miner Res. 24(2):182-195. 2009. 3. Cummings SR, San Martin J, McClung MR, et al. N Engl J Med. 361(8):756-765. 2009. 4. Eastell R, Christiansen C, Grauer A, et al. J Bone Miner Res. 26(3):530-537. 2011. 5. Simon JA, Recknor C, Moffett AH Jr, et al. Menopause. 20(2):130-137. 2013. 6. Bone HG, Wagman RB, Brandi ML, et al. Lancet Diabetes Endocrinol. 5(7):513-523. 2017. Technical ProtocolsCertificate of Analysis | 
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Formats Available
| Prod No. | Description | 
|---|---|
| LT2800 | |
| LT2805 | 
 Products are for research use only. Not for use in diagnostic or therapeutic procedures.
Products are for research use only. Not for use in diagnostic or therapeutic procedures.

 
	
		 
		



