Anti-Human PD-1 (Spartalizumab)
Anti-Human PD-1 (Spartalizumab)
Product No.: P450
Product No.P450 Clone PDR001 Target PD-1 Product Type Biosimilar Recombinant Human Monoclonal Antibody Alternate Names CD279, PD1, Anti-PD1, PDCD1 Isotype Human IgG4κ Applications ELISA , FA , FC , IP , WB |
Antibody DetailsProduct DetailsReactive Species Human Host Species Human Expression Host HEK-293 Cells FC Effector Activity Active Immunogen Human PD-1 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 ? ELISA, WB, IP, FA, FC 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 Spartalizumab. This product is for research use only. Spartalizumab activity is directed against human PD-1. Background PD-1 is a transmembrane protein in the CD28/CTLA-4 subfamily of the Ig superfamily 1, 2 . When stimulated via the T cell receptor (TCR), Tregs translocate PD-1 to the cell surface 3. Programmed cell death 1 ligand 1 (PD-L1; CD274; B7H1) and programmed cell death 1 ligand 2 (PD-L2; CD273; B7DC) have been identified as PD-1 ligands 1. PD-1 is co-expressed with PD-L1 on tumor cells and tumor-infiltrating antigen-presenting cells (APCs) 2 . Additionally, PD-1 is co-expressed with IL2RA on activated CD4 + T cells 3 . PD-1 is an immune checkpoint receptor that suppresses cancer-specific immune responses 4. Additionally, PD-1 acts as a T cell inhibitory receptor and plays a critical role in peripheral tolerance induction and autoimmune disease prevention as well as important roles in the survival of dendritic cells, macrophage phagocytosis, and tumor cell glycolysis 2. PD-1 prevents uncontrolled T cell activity, leading to attenuation of T cell proliferation, cytokine production, and cytolytic activities. Additionally, the PD-1 pathway is a major mechanism of tumor immune evasion, and, as such, PD-1 is a target of cancer immunotherapy 2. Spartalizumab is a humanized IgG4 anti-PD1 antibody that has been tested for the treatment of various cancers 5, 6. Spartalizumab binds PD-1 with sub-nanomolar affinity and blocks interactions with ligands PD-L1 and PD-L2, leading to T cell activation 5. Antigen Distribution PD-1 is expressed on activated T cells, B cells, a subset of thymocytes,
macrophages, dendritic cells, and some tumor cells and is also retained in the intracellular
compartments of regulatory T cells (Tregs).
Ligand/Receptor PD-L1, CD274 NCBI Gene Bank ID UniProt.org Research Area Biosimilars . Cancer . Immuno-Oncology . Immunology 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 Spartalizumab biosimilars are used as calibration standards or reference controls in pharmacokinetic (PK) bridging ELISA assays to ensure accurate, precise, and comparable measurement of drug concentration across both biosimilar and reference serum samples. This approach supports robust PK bioequivalence assessments. Key Points on Their Use:
Summary Table: How Research-Grade Spartalizumab Biosimilars are Used in PK Bridging ELISA
In summary: Research-grade Spartalizumab biosimilars, when used as calibration standards and reference controls, enable the robust quantification and direct comparison of PK profiles between biosimilar and reference drug in bridging ELISA formats for serum samples, underpinned by rigorous calibration, validation, and regulatory alignment. The primary models used to study in vivo efficacy of research-grade anti-PD-1 antibodies, focusing on tumor growth inhibition and characterization of tumor-infiltrating lymphocytes (TILs), are syngeneic mouse models and humanized mouse models. The choice depends on whether the antibody targets mouse or human PD-1. 1. Syngeneic Mouse Models
2. Humanized Mouse Models
Summary Table:
Key Points:
Both model types are prominent in preclinical immuno-oncology research for dissecting anti-PD-1 efficacy and TIL biology. Researchers are actively investigating spartalizumab, a humanized IgG4 anti-PD-1 monoclonal antibody, in combination with other checkpoint inhibitors to explore synergistic effects in immune-oncology models. The most extensively studied combination involves spartalizumab with anti-LAG-3 inhibitors, particularly in advanced solid malignancies. LAG-3 and PD-1 Combination StudiesThe combination of spartalizumab with ieramilimab, an anti-LAG-3 antibody, represents one of the most promising approaches in dual checkpoint inhibition research. Ieramilimab is a humanized IgG4 monoclonal antibody that inhibits LAG-3 interaction with MHC class II molecules, while spartalizumab blocks PD-1 interaction with its ligands PD-L1 and PD-L2. This combination targets two critical pathways involved in T-cell exhaustion and immune suppression. In multicenter, open-label phase 2 studies, researchers have evaluated this combination across multiple cancer types including non-small cell lung cancer (NSCLC), melanoma, triple-negative breast cancer (TNBC), renal cell carcinoma (RCC), and mesothelioma. The rationale for this combination stems from the understanding that LAG-3 and PD-1 co-regulate T-cell exhaustion and that compensatory upregulation of LAG-3 has been linked to adaptive resistance to PD-1 checkpoint blockade. Mechanisms of Synergistic ActionThe synergistic effects observed in these combination studies operate through several key mechanisms. First-in-human dose-escalation trials have demonstrated that the ieramilimab-spartalizumab combination enhances T-cell activation in the tumor microenvironment. Specifically, combination treatment increases LAG-3 gene expression and T-cell-inflamed signature genes in most patients, suggesting enhanced immune activation compared to single-agent therapy. The therapeutic approach addresses multiple immune-mediated resistance mechanisms simultaneously, including T-cell dysfunction marked by enhanced expression of co-inhibitory receptors, decreased T-cell priming and infiltration, and suppression mediated by regulatory T cells and myeloid-derived suppressor cells. Safety Profile and TolerabilityA critical advantage of the spartalizumab-ieramilimab combination is its favorable safety profile. Unlike combination checkpoint blockade with anti-CTLA-4 and anti-PD-1 agents, the immune-mediated toxicity of ieramilimab combined with spartalizumab was comparable to that seen with spartalizumab alone. Phase 1 studies showed no increase in incidence of immune-mediated serious adverse events, with the most commonly occurring treatment-related adverse events being low-grade fatigue, gastrointestinal side effects, pruritus, and fever. Biomarker-Driven Patient SelectionResearchers utilize sophisticated biomarker analyses to identify patient populations most likely to benefit from combination therapy. Studies have shown that patients with higher expression of T-cell-inflamed gene signatures in baseline tumor samples were more likely to respond to the ieramilimab-spartalizumab combination. Interestingly, LAG-3 expression by immunohistochemistry did not predict benefit of dual LAG-3/PD-1 blockade, though LAG-3 gene expression by RNA sequencing was associated with treatment response. Comparative Mechanism StudiesResearch has also examined how different checkpoint inhibitor combinations operate through distinct mechanisms. Studies comparing anti-PD-1/CTLA-4 versus anti-PD-1/LAG-3 treatments in advanced melanoma have identified different subtypes of immune cells activated by each combination, providing insights into their unique mechanisms of action. Clinical Trial Design and Efficacy AssessmentThe clinical development of these combinations follows rigorous phase 1/2 study designs that assess safety, pharmacokinetics, and preliminary efficacy in patients with advanced or metastatic solid tumors. Researchers evaluate both treatment-naive patients and those previously treated with PD-1/PD-L1 inhibitors to understand the potential for overcoming resistance mechanisms. The research demonstrates that while single-agent anti-LAG-3 therapy shows limited anti-tumor activity in solid tumors, the combination approach with PD-1 inhibition provides a promising strategy for enhancing immune checkpoint blockade efficacy and overcoming resistance mechanisms in complex immune-oncology models. A Spartalizumab biosimilar can be employed as both the capture and detection reagent in a bridging anti-drug antibody (ADA) ELISA to detect and monitor anti-Spartalizumab immune responses in patients treated with the reference or biosimilar drug. How this works:
Assay setup:
Therefore, positive signal is generated only if the patient sample contains antibodies capable of binding simultaneously to two molecules of Spartalizumab—i.e., true anti-drug antibodies. Summary table: Key rationale for biosimilar use:
Caveats:
In summary, a Spartalizumab biosimilar serves as both the capture and detection reagent in a bridging ADA ELISA, exploiting the bivalency of patient ADAs to monitor immune responses against the therapeutic, with the assay design being widely accepted for immunogenicity testing of biosimilars and their reference products. References & Citations1 Matsumoto K, Inoue H, Nakano T, et al. J Immunol. 172(4):2530-2541. 2004. 2 Zhao Y, Harrison DL, Song Y, et al. Cell Rep. 24(2):379-390.e6. 2018. 3 Raimondi G, Shufesky WJ, Tokita D, et al. J Immunol. 176(5):2808-2816. 2006. 4 Pardoll DM. Nat Rev Cancer. 12(4):252-264. 2012. 5 Kaplon H, Reichert JM. MAbs. 11(2):219-238. 2019. 6 Dummer R, Long GV, Robert C, et al. J Clin Oncol. 40(13):1428-1438. 2022. Technical ProtocolsCertificate of Analysis |
Formats Available
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P450 | |
P455 |
