Anti-Human PD-1 (Tislelizumab) – Fc Muted™

Anti-Human PD-1 (Tislelizumab) – Fc Muted™

Product No.: P805

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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

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Antibody Details

Product Details

Reactive 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.

Description

Description

Specificity
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 Advisor

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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:

  • The biosimilar (non-clinical research grade) is serially diluted to produce a range of known concentrations, which are usually lyophilized for stability and reproducibility.
  • These standards are spiked into human serum or plasma matrices to model the sample environment, minimizing matrix effects and optimizing dilutional linearity.
  • PK bridging ELISAs typically use sandwich assays with anti-idiotypic monoclonal antibodies for capture and detection, ensuring specificity for Tislelizumab and accurate discrimination from endogenous immunoglobulins or other therapeutics.
  • The biosimilar is validated for analytical equivalence to the originator (innovator) drug, often calibrated against both international standards (e.g., from NIBSC) and commercial reference drugs.
  • Quantitative assays compare sample signals to a calibration curve derived from the biosimilar reference, facilitating reliable pharmacokinetic measurements.
  • Rigorous assay validation—including intra/inter-assay precision, specificity, accuracy, and sensitivity—is performed across multiple concentrations, users, and days. Precision targets such as <10% coefficient of variation (CV) are typical.

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:

  • Research-use Tislelizumab biosimilars are not intended for clinical diagnostics.
  • Using biosimilar standards supports bridging ELISAs, which are essential for demonstrating bioanalytical comparability in biosimilar drug development programs.
  • Standards may be routinely requalified against global benchmarks to ensure robustness, and standard curve parameters (such as limit of detection and dynamic range) are clearly specified in kit documentation.

Summary Table: Research-Grade Tislelizumab Biosimilar in PK Bridging ELISA

RoleApplication Details
Calibration StandardSerially diluted to build standard curves; lyophilized format
Reference ControlValidates assay performance and quantifies QC samples
Matrix SpikingAdded to serum/plasma for matrix effect studies
Analytical ValidationCalibrated against innovator drug & international standards
Assay SpecificityEnsured by anti-idiotypic antibodies
QuantitationEnables PK measurement of serum Tislelizumab concentration
ComplianceFollows FDA/EMA/ICH bioanalytical guidelines

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 Models

MC38 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 Models

NSG 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 Methods

These 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 Combinations

Researchers 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 Approaches

Novel 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 Studies

The 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 Directions

While 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 Testing

Overview

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

  • Capture Reagent: The Tislelizumab biosimilar (or reference) is biotinylated and immobilized on streptavidin-coated plates. This captures any ADA (anti-drug antibodies) present in patient serum that specifically recognize Tislelizumab, regardless of whether the drug is the reference or the biosimilar.
  • Detection Reagent: A second Tislelizumab molecule (either reference or biosimilar), labeled with a detection tag (e.g., horseradish peroxidase, HRP), is added. This molecule binds to the captured ADAs, forming a “bridge.” The resulting signal quantifies the amount of ADA present.
  • Biosimilar as Both Capture and Detection: To specifically monitor patient immune responses against the biosimilar, the biosimilar itself can be used for both capture and detection. This ensures the assay detects antibodies elicited by the biosimilar, providing a direct measure of its immunogenicity.

Application in Patient Monitoring

  • Immunogenicity Assessment: By using the biosimilar as both reagents, the bridging ELISA directly assesses whether patients develop antibodies against the biosimilar, which could affect drug efficacy or safety.
  • Comparison to Reference Product: In regulatory and clinical studies, the immunogenicity profile of the biosimilar (as measured by ADA incidence and titers) is compared to that of the reference product to confirm biosimilarity.
  • Clinical Relevance: Detection of ADAs is important because they can lead to loss of drug efficacy, hypersensitivity, or other adverse effects.

Key Technical Considerations

  • Specificity and Sensitivity: The bridging ELISA format is highly sensitive and specific when optimized, but matrix effects and drug interference can impact results. Proper controls and assay validation are essential.
  • Reagent Choice: The use of the biosimilar as both capture and detection reagents ensures that the assay is specific for antibodies against the biosimilar itself, not just the reference molecule.
  • Regulatory Context: Demonstrating a matching immunogenicity profile between biosimilar and reference is part of the “totality of evidence” approach required for biosimilar approval.

Summary Table: Use of Tislelizumab Biosimilar in Bridging ADA ELISA

Assay StepReagent UsedPurpose
CaptureBiotinylated Tislelizumab biosimilarImmobilize ADA from patient serum
DetectionLabeled Tislelizumab biosimilarQuantify bound ADA via enzymatic reaction
SpecificityBiosimilar for both stepsDirectly measure anti-biosimilar antibodies

Conclusion

In 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 & Citations

1. 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.
Indirect Elisa Protocol
FA
Flow Cytometry
General Western Blot Protocol

Certificate of Analysis

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Disclaimer AlertProducts are for research use only. Not for use in diagnostic or therapeutic procedures.