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]。