Toripalimab是一种重组人源化抗PD-1单克隆抗体。
Cas No.:1924598-82-2
Sample solution is provided at 25 µL, 10mM.
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Toripalimab is a recombinant humanized anti-PD-1 monoclonal antibody. Toripalimab binds to the PD-1 receptor on the surface of T cells, blocking PD-1 interaction with the ligands PD-L1 and PD-L2, thereby alleviating the PD-1 signaling pathway-mediated immune suppression[1-2]. Toripalimab can be used in research related to cancers such as melanoma, urothelial carcinoma, nasopharyngeal carcinoma, and esophageal squamous cell carcinoma[3-4].
In vitro, treatment of SEB-stimulated human peripheral blood mononuclear cells (PBMCs) with Toripalimab (3.3-10µg/mL) for 3 days, or treatment of anti-CD3/anti-CD28 stimulated human naïve CD8+ T cells for 3 days. Toripalimab significantly enhanced the secretion of Th1 cytokines (IFN-γ, IL-2, TNF) and myeloid-derived inflammatory cytokines (IL-1α, IL-1β), while also enhancing T cell activation. In ex vivo cultures of dissociated tumor cells from NSCLC patients, treatment with Toripalimab (10µg/mL) combined with anti-CD3/anti-CD28 stimulation for 6-24 hours significantly upregulated IFN-γ production and the expression of genes related to immune cell pathways[5]. Treatment of human PBMCs with Toripalimab (0.01-10µg/mL) for 6-10 days, Toripalimab stimulated human T cell proliferation in a dose-dependent manner and enhanced the secretion of IFN-γ and TNF-α[6].
In vivo, C57/hPD-1 knock-in mice bearing MC38 tumors were treated with Toripalimab (0.3-10mg/kg, intraperitoneal injection, twice weekly) for 3 weeks. Toripalimab significantly inhibited tumor growth in a dose-dependent manner[7]. hPD-1 knock-in mice subcutaneously inoculated with B16-vec or B16-IL33 melanoma cells were treated with Toripalimab (200µg/100µL, twice weekly, for 3 weeks). The combination of Toripalimab and IL-33 significantly suppressed tumor growth and prolonged the survival of tumor-bearing mice[8].
References:
[1] Zhang X, Zheng J, Niu Y, et al. Long-term survival in extensive-stage small-cell lung cancer treated with different immune checkpoint inhibitors in multiple-line therapies: A case report and literature review. Front Immunol. 2022 Nov 30;13:1059331.
[2] Thuss-Patience P, Stein A. Immunotherapy in Squamous Cell Cancer of the Esophagus. Curr Oncol. 2022 Mar 30;29(4):2461-2471.
[3] Lian D, Yang Y, Gan Y, et al. Cost-effectiveness of toripalimab plus chemotherapy versus chemotherapy as first-line treatment for advanced non-small cell lung cancer in China: a societal perspective. Expert Rev Pharmacoecon Outcomes Res. 2025 Apr;25(4):587-596.
[4] Zhang L, Hao B, Geng Z, et al. Toripalimab: the First Domestic Anti-Tumor PD-1 Antibody in China. Front Immunol. 2022 Jan 12;12:730666.
[5] Rajasekaran N, Wang X, Ravindranathan S, et al. Toripalimab, a therapeutic monoclonal anti-PD-1 antibody with high binding affinity to PD-1 and enhanced potency to activate human T cells. Cancer Immunol Immunother. 2024 Feb 24;73(3):60.
[6] Fu J, Wang F, Dong LH, et al. Preclinical evaluation of the efficacy, pharmacokinetics and immunogenicity of JS-001, a programmed cell death protein-1 (PD-1) monoclonal antibody. Acta Pharmacol Sin. 2017 May;38(5):710-718.
[7] Liu H, Guo L, Zhang J, et al. Glycosylation-independent binding of monoclonal antibody toripalimab to FG loop of PD-1 for tumor immune checkpoint therapy. MAbs. 2019 May/Jun;11(4):681-690.
[8] He H, Shi L, Meng D, et al. PD-1 blockade combined with IL-33 enhances the antitumor immune response in a type-1 lymphocyte-mediated manner. Cancer Treat Res Commun. 2021;28:100379.
Toripalimab是一种重组人源化抗PD-1单克隆抗体。Toripalimab可与T细胞表面的PD-1受体结合，阻断PD-1与配体PD-L1和PD-L2的相互作用，从而消除PD-1信号通路介导的免疫抑制[1-2]。Toripalimab可用于黑色素瘤、尿路上皮癌、鼻咽癌和食管鳞癌等癌症的相关研究[3-4]。
在体外，Toripalimab（3.3-10µg/mL）处理SEB（100ng/mL）刺激的人外周血单个核细胞（PBMCs）3天，或处理抗CD3/抗CD28刺激的CD8+ T细胞3天。Toripalimab显著增强IFN-γ、IL-2、TNF等Th1细胞因子及IL-1α、IL-1β等骨髓源性炎症细胞因子的分泌，同时增强T细胞活化。在离体培养的NSCLC患者肿瘤解离细胞中，Toripalimab（10µg/mL）处理并结合抗CD3/抗CD28刺激6-24小时，可显著上调IFN-γ产生及免疫细胞通路相关基因的表达[5]。Toripalimab（0.01-10μg/mL）处理人外周血单个核细胞（PBMCs）6-10天，剂量依赖性地刺激人T细胞增殖，同时增强IFN-γ和TNF-α的分泌[6]。
在体内，Toripalimab（0.3-10mg/kg）每周两次腹腔注射处理接种了MC38肿瘤细胞的C57/hPD-1基因敲入小鼠3周。Toripalimab以剂量依赖的方式显著抑制了肿瘤生长[7]。Toripalimab（200μg/100μL；每周两次；连续处理3周）处理皮下接种了B16-vec或B16-IL33黑色素瘤细胞的hPD-1基因敲入小鼠。Toripalimab与IL-33联合显著抑制了肿瘤生长并延长了荷瘤小鼠的生存期[8]。
| Cell experiment [1]: | |
Cell lines | Human peripheral blood mononuclear cell (PBMC)-derived T cells |
Preparation Method | Human PBMCs were isolated and cultured for six days in the presence of IL-4 and GM-CSF to generate immature dendritic cells (imDCs). The imDCs were then incubated with TNF-α for three days to obtain mature dendritic cells (mDCs). T cells were isolated from the PBMCs of the same donors and labeled with CFSE. The mDCs, T cells, and Tetanus Toxoid (10ng/mL) were mixed. Different concentrations of Toripalimab (0.01 to 10μg/mL), Nivolumab (positive control), or hIgG4 (negative control) were added to the mixtures. |
Reaction Conditions | 0.01 to 10μg/mL; 10 days. |
Applications | Treatment with Toripalimab dose-dependently stimulated human T cell proliferation, as well as IFN-γ and TNF-α secretion. Toripalimab was more effective in promoting T cell proliferation and cytokine secretion at concentrations of 0.1-3μg/mL. |
| Animal experiment [2]: | |
Animal models | hPD-1 knock-in mice with a C57BL/6 background (C57/hPD-1 mice) |
Preparation Method | Mice were subcutaneously inoculated with 1 x 106 MC38 syngeneic tumor cells on day 0. On day 6, the inoculated mice were randomized into groups and treated via intraperitoneal injection with either control IgG, saline, or Toripalimab at 0.3-10mg/kg. |
Dosage form | 0.3-10mg/kg; i.p.; twice a week for 3 weeks. |
Applications | Toripalimab inhibited tumor growth in a dose-dependent manner, with substantial antitumor efficacy observed at doses of 1, 3, and 10mg/kg. |
References: | |
| Cas No. | 1924598-82-2 | SDF | Download SDF |
| 别名 | 特瑞普利单抗 | ||
| 分子式 | 分子量 | 147.3 kDa | |
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