Anti-Human PD-1 (Tislelizumab) – Fc Muted™
Anti-Human PD-1 (Tislelizumab) – Fc Muted™
Product No.: P805
Product No.P805 Clone BGB-A317 Target PD-1 Product Type Biosimilar Recombinant Human Monoclonal Antibody Alternate Names Anti-PD-1, PDCD1, CD279 Isotype Human IgG4κ Applications ELISA , FA , FC , WB |
Antibody DetailsProduct DetailsReactive Species Human Host Species Human Expression Host HEK-293 Cells FC Effector Activity Muted Recommended Isotype Controls 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. 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 Applications and Recommended Usage? Quality Tested by Leinco ELISA, WB Additional Applications Reported In Literature ? FA, ELISA Cap, 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 Tislelizumab. This product is for research use only. Tislelizumab activity is directed against human PD-1 (CD274). Background Programmed cell death 1 (PD-1) is a transmembrane protein in the Ig superfamily1,2 that acts as an immune checkpoint receptor3, a T cell inhibitory receptor, plays critical roles in peripheral tolerance induction, autoimmune disease prevention, macrophage phagocytosis, tumor cell glycolysis, and dendritic cell survival2. 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 immunotherapy2. Programmed cell death 1 ligand 1 (PD-L1; CD274; B7H1) and programmed cell death 1 ligand 2 (PD-L2; CD273; B7DC) are ligands1.
Tislelizumab was developed by BeiGene as an immunotherapeutic for hematological cancers and advanced solid tumors4. Tislelizumab is a humanized mouse monoclonal antibody designed as a synthetic protein fusion of the 317-4B6 heavy chain VH fragment with human γ4 chain clone mut10 effector/constant domain fragment (disulfide with anti-human PD-1) and synthetic clone 317-4B6 light chain VL fragment with human κ chain constant region fragment, dimer4,5. Tislelizumab binds to PD-1 with high specificity and affinity using the critical epitopes Gln75, Thr76, Asp77 and Arg86, blocking PD-1 and preventing ligand binding4. The epitope is located on the CC’ loop of the front β sheet face of PD-1 and causes stereospecific hindrance to PD-L1 binding6. Unlike other IgG4 anti-PD-1 blocking antibodies, the S228P mutation known to bind to Fc-γ receptor 1 (FcγRI) and induce antibody-dependent cellular phagocytosis of T cells is not present4 and several mutations in the Fc-hinge region render tislelizumab unable to bind to FcγRs generally6. Consequently, tislelizumab has low affinity for FcγRI and baseline antibody-dependent cellular phagocytosis relative to control antibodies4. Additionally, FcR-mediated effects such as antibody-dependent cell-mediated cytotoxicity or compliment-dependent cytotoxicity are not observed4,6. 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-1, CD279 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 Tislelizumab biosimilars are used in PK bridging ELISA assays primarily as calibration standards or reference controls to quantify drug concentration in serum samples, ensuring consistent, accurate measurement across biosimilar and innovator products. These biosimilars act as the reference material for constructing standard curves during the assay:
Best practice, according to regulatory guidance and industry consensus, is to validate a single PK assay using a unified analytical standard for all test and reference products, facilitating direct comparison and minimizing confounding variability. Additional context:
Summary Table: Research-Grade Tislelizumab Biosimilar in PK Bridging ELISA
In summary, research-grade biosimilars of Tislelizumab ensure that PK bridging ELISAs can accurately and reproducibly measure drug concentrations in serum, supporting regulatory comparability studies and robust bioanalytical validation. The research literature describes several well-established syngeneic and humanized mouse models used to study anti-PD-1 antibody efficacy in tumor growth inhibition and characterize tumor-infiltrating lymphocytes (TILs). Syngeneic Mouse ModelsMC38 Colon Adenocarcinoma Model represents one of the most extensively used models for anti-PD-1 research. This model demonstrates robust sensitivity to anti-PD-1 treatment and has been instrumental in developing resistance models through serial passaging in anti-PD-1 treated mice. The MC38 model is particularly valuable for studying mechanisms of both sensitivity and acquired resistance to checkpoint blockade. Melanoma Models include multiple variants used for anti-PD-1 studies. The TyrNras melanoma model has been developed with acquired resistance to anti-PD-1 antibodies through serial treatment cycles. Additionally, melanoma models have been used extensively to study combination therapies, such as the combination of hydroxychloroquine (HCQ) with anti-PD-1 antibodies, which showed enhanced antitumor efficacy and improved survival. Bladder Cancer Models encompass both MB49 and MBT2 bladder cancer cell lines, which have been adapted to create variants with acquired resistance to anti-PD-1 and/or PD-L1 antibodies. These models provide insight into the heterogeneous mechanisms of resistance encountered clinically. Additional Syngeneic Models include several other well-characterized systems. The RENCA kidney cancer model has been used to develop anti-PD-1 resistant variants. The Hepa1-6 hepatocellular carcinoma model, CT26 colorectal cancer model, and EMT-6 mammary carcinoma model are all known to be sensitive or partially sensitive to anti-PD-1 treatment. These models allow researchers to study different intrinsic tumor-immunity cycles and characterize distinct TIL profiles. Humanized Mouse ModelsNSG Humanized Mouse Models utilize non-obese diabetic scid gamma (NSG) mice engrafted with human immune cells to test humanized anti-PD-1 antibodies. These models have been used with human tumor cell lines including PC-3 prostate cancer and HCT-116 colorectal cancer xenografts. The humanized models are engrafted with allogeneic human T cells and monocyte-derived dendritic cells to create a more clinically relevant immune microenvironment. Humanized Target Knock-in Models represent an advanced approach where specific human targets are knocked into mouse models to enable testing of fully human antibodies while maintaining the syngeneic tumor environment. These models have proven instrumental for evaluating immunotherapy bioactivity in vivo. Applications and Characterization MethodsThese models enable comprehensive characterization of the tumor immune microenvironment through spectral cytometry to analyze tumor immune infiltrates, focusing on both lymphoid and myeloid subpopulations. Researchers use these platforms to study various immune cell depletion strategies, including removal of CD8+ cytotoxic T lymphocytes, CD4+ T cells, CD25+ regulatory T cells, NK cells, and macrophages to understand the contribution of different immune cell types to anti-PD-1 efficacy. The models also facilitate investigation of combination therapies and resistance mechanisms. For example, studies have explored combinations with PPT1 inhibitors that enhance T cell-mediated cytotoxicity through macrophage phenotype switching from M2 to M1 and reduction of myeloid-derived suppressor cells. Additionally, resistant variants enable investigation of novel therapeutic approaches, such as local mRNA-based immunotherapy that can overcome resistance to systemic checkpoint blockade. These diverse model systems collectively provide a comprehensive platform for understanding anti-PD-1 mechanisms of action, resistance pathways, and potential combination strategies across multiple cancer types. Based on the available research, tislelizumab is not actually a biosimilar but rather an original anti-PD-1 monoclonal antibody developed by BeiGene. However, researchers are actively investigating its use in combination with other checkpoint inhibitors to study synergistic effects in immune-oncology applications. Current Research on Tislelizumab CombinationsResearchers are exploring tislelizumab in combination therapies based on the principle that combining immune checkpoint inhibitors may help overcome resistance pathways and improve sensitivity to PD-1/PD-L1 therapy. The rationale is that such combinations could enhance efficacy while minimizing drug toxicity by potentially reducing dosages and shortening treatment duration. Documented Combination ApproachesNovel PD-L1 Inhibitor Combinations: In a phase 1/2 clinical study, researchers combined BGB-A333 (a novel PD-L1 inhibitor) with tislelizumab, which demonstrated promising antitumor effects without increasing the risk of immune-related adverse events (irAEs). This represents a dual checkpoint blockade approach targeting both PD-1 and PD-L1 pathways simultaneously. Safety Profile Advantages: Tislelizumab exhibits a significantly lower signal for immune-related adverse events compared to other checkpoint inhibitors, with a reporting odds ratio (ROR) of 1.69. This compares favorably to anti-PD-1 inhibitors like nivolumab (OR 2.21) and pembrolizumab (OR 2.35), anti-PD-L1 inhibitors like atezolizumab (OR 2.27), and anti-CTLA-4 inhibitors like ipilimumab (OR 3.01). Clinical Rationale for Combination StudiesThe superior safety profile makes tislelizumab an attractive candidate for combination therapy studies. For patient populations at high risk of immune-related adverse events, researchers suggest that immune therapy regimens based on tislelizumab may be superior to other checkpoint inhibitors and could become the preferred option. Research Gaps and Future DirectionsWhile the search results indicate that further research is urgently needed to explore immune checkpoint inhibitor combination regimens based on tislelizumab, specific studies combining tislelizumab with anti-CTLA-4 or anti-LAG-3 inhibitors are not detailed in the current literature. The field appears to be in the early stages of exploring these synergistic combinations, with most documented research focusing on PD-1/PD-L1 dual blockade approaches rather than the broader combination strategies with CTLA-4 or LAG-3 inhibitors. Role of Tislelizumab Biosimilar in Bridging ADA ELISA for Immunogenicity TestingOverview Anti-Drug Antibody (ADA) bridging ELISA is a sensitive assay used to detect and quantify immune responses against biologic drugs, such as monoclonal antibodies like Tislelizumab, in patient serum. When evaluating biosimilars, this assay is critical for demonstrating that the immunogenicity profile of the biosimilar matches that of the reference product. The biosimilar can be used either as the capture reagent, the detection reagent, or both, depending on the assay design. Assay Design and Biosimilar Use
Application in Patient Monitoring
Key Technical Considerations
Summary Table: Use of Tislelizumab Biosimilar in Bridging ADA ELISA
ConclusionIn a bridging ADA ELISA for immunogenicity testing, a Tislelizumab biosimilar can be used as both the capture and detection reagent to specifically monitor a patient’s immune response against the biosimilar. This approach allows direct assessment of ADA development, supports biosimilarity evaluations, and helps ensure patient safety and therapeutic efficacy. Proper assay design and validation are critical to obtaining reliable, clinically meaningful results. 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. Pardoll DM. Nat Rev Cancer. 12(4):252-264. 2012. 4. Lee A, Keam SJ. Drugs. 80(6):617-624. 2020. 5. https://searchusan.ama-assn.org/usan/documentDownload?uri=/unstructured/binary/usan/tislelizumab.pdf 6. Zhang L, Geng Z, Hao B, et al. Cancer Control. 29:10732748221111296. 2022. 7. Zhang T, Song X, Xu L, et al. Cancer Immunol Immunother. 67(7):1079–90. 2018. 8. Zhang T, Song J, Li Y, et al. Cancer Research Conference: 107th AACR Annual Meeting 2016;76(Suppl 14). 9. Desai J, Deva S, Lee JS, et al. J Immunother Cancer. 8(1):e000453. 2020. 10. Song Y, Gao Q, Zhang H, et al. Leukemia. 34(2):533-542. 2020. 11. Hong Y, Feng Y, Sun H, et al. FEBS Open Bio. 11(3):782-792. 2021. Technical ProtocolsCertificate of Analysis |
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