Nivolumab (anti-PD-1)

製品コードA2002 別名: BMS-936558, ONO-4538, MDX-1106

For research use only. Not for use in humans.

Nivolumab is a genetically engineered, fully human immunoglobulin (Ig) G4 monoclonal antibody directed against the negative immunoregulatory human cell surface receptor programmed death-1 (PD-1,PCD-1) with immune checkpoint inhibitory and antineoplastic activities. MW : 143.597 KD.

サイズ 価格(税別)  
JPY 117362.00

文献中Selleckの製品使用例(3)

質量管理及び製品安全説明書

PD-1/PD-L1阻害剤の選択性比較

生物活性

製品説明 Nivolumab is a genetically engineered, fully human immunoglobulin (Ig) G4 monoclonal antibody directed against the negative immunoregulatory human cell surface receptor programmed death-1 (PD-1,PCD-1) with immune checkpoint inhibitory and antineoplastic activities. MW : 143.597 KD.
ターゲット
PD-1/PD-L1 interaction [2]
(Cell-free assay)
PD-1/PD-L2 interaction [2]
(Cell-free assay)
2.52 nM 2.59 nM
体外試験

Nivolumab (anti-human PD-1) binds PD-1 with high affinity (KD 2.6 nmol/l by Scatchard analysis to polyclonally activated human T cells) and blocks its interactions with both B7-H1 and B7-DC[1]. It effectively inhibits the interaction between PD-1 and its ligands. In vitro assays demonstrated the ability of nivolumab to potently enhance T-cell responses and cytokine production in the mixed lymphocyte reaction and superantigen or cytomegalovirus stimulation assays. Nivolumab inhibits the interaction between PD-1 and its ligands, PD-L1 and PD-L2, with IC50 values of 2.52 and 2.59 nmol/L, respectively, as shown by surface plasmon resonance. In a study using FACS to evaluate ligand binding to PD-1 expressed on CHO cells, the IC50 values for nivolumab-mediated inhibition of PD-1 binding to PD-L1 or PD-L2 were similar (1.04 and 0.97 nmol/L, respectively). Nivolumab binds specifically to PD-1 and not to other immunoglobulin superfamily proteins, such as CD28, CTLA-4, ICOS, and BTLA. Nivolumab can, at very low concentrations (∼1.5 ng/mL), enhance T-cell reactivity in the presence of a T-cell receptor stimulus. However, nivolumab had no stimulatory effect in the absence of antigen or T-cell receptor stimulus. Specifically, there was no significant release of inflammatory cytokines, including IFNγ, TNFα, IL-2, IL-4, IL-6, or IL-10, from unstimulated whole blood after coincubation with nivolumab. Nivolumab does not cause nonspecific lymphocyte activation[2].

体内試験 Nivolumab (anti-human PD-1) is well tolerated, dose-limiting toxicities (DLTs) were not reached and the maximum tolerable dose (MTD) was not defined in patients with advanced stage solid tumors. The measured half-life of nivolumab was 12-20 days, the pharmacodynamic effects of PD-1 receptor occupancy was even more prolonged at 85 days, indicating the biological durability of this high-affinity mAb[1]. In monkeys, serum nivolumab has a relatively slow clearance with limited extra vascular distribution, as demonstrated by a Vss value consistent with plasma volume. Mean apparent terminal elimination half-life estimates for males and females at 1 mg/kg were similar (124 and 139 hours, respectively), and the mean half-life estimate for males at 10 mg/kg was 261 hours. Although nivolumab seems to lack toxicity in monkeys, toxicities have been observed in human clinical trials. In a phase I trial, nivolumab had a favorable safety profile. Adverse events were generally similar to those observed with ipilimumab, although with lower incidence and of less severity, and comprised gastrointestinal, endocrine, and skin toxicities, and pulmonary inflammation. Interestingly, pneumonitis has been observed in PD-1-deficient mice bred onto the MRL genetic background, but not in PD-1-deficient mice with other genetic backgrounds[2].

お薦めの試験操作(参考用のみ)

細胞試験:
+ 展開
  • Objective: Antigen-specific recall response in vitro
    Cells: PBMCs
    Concentrations: 0-10 μM
    Incubation Time: 4 days
    Method: In a cytomegalovirus (CMV)-restimulation assay, 2 × 105 PBMCs from a CMV-positive donor (Astarte) were stimulated using lysate of CMV-infected cells (Astarte), with serial dilutions of nivolumab added at the initiation of the assay. After 4 days, supernatants were assayed for IFNγ.
    Reference: http://cancerimmunolres.aacrjournals.org/content/2/9/846

    Objective: Mixed lymphocyte response (MLR) assays
    Cells: Monocyte-derived DC and CD4+ T cells
    Concentrations: 50 mg/mL to 5 ng/mL
    Incubation Time: 6 days
    Method: Mixed lymphocyte response assays were performed by co-culturing 1×105 cells CD4+ T cells with allogeneic monocyte-derived dendritic cells (DC) at a ratio of 10:1 (T:DC) in flat-bottom 96-well microtiter plates. CD4+ T cells and DC were incubated for 6 days in the presence or absence of nivolumab titrated 1:10 from 50 mg/mL to 5 ng/mL along with ipilimumab at 0, 5, or 50 μg/mL. Culture supernatants were harvested on day 5 for ELISA analysis of IFN-γ secretion.
    Reference: https://www.ncbi.nlm.nih.gov/pubmed/27610613

    Nivolumab can apply to humanized mice (eg Rag2-/-IL2Rgnull mice), peripheral blood and other related assays (Only for Reference)

動物試験:
+ 展開
  • Objective: pharmacokinetic (PK) study
    Animal Models: Cynomolgus monkeys (Macaca fascicularis)
    Formulation: Saline
    Dosages: 3 mg/kg or 10 mg/kg
    Administration: i.v.
    Reference: http://cancerimmunolres.aacrjournals.org/content/2/9/846

    Objective: To determine that nivolumab and urelumab enhance antitumor activity in mice model
    Animal Models: Rag2-/-IL2Rgnull mice (humanized mice) were injected with 1×107 human PBMCs intraperitoneally (i.p.) and a total of 3.5×106 HT29 human colon carcinoma cells subcutaneously (s.c.)
    Formulation: saline
    Dosages: 200 μg per injection
    Administration: i.v.
    Reference: https://www.ncbi.nlm.nih.gov/pubmed/26113085

    Nivolumab can apply to humanized mice (eg Rag2-/-IL2Rgnull mice), peripheral blood and other related assays (Only for Reference)

製品説明

Formulation PBS buffer, pH 7.2
Isotype Human IgG4
Source CHO cells
Storage Store at -80°C and avoid freeze-thaw cycles.

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Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID