Abstract
Toripalimab (Tuoyi™) is a selective, recombinant, humanized monoclonal antibody against programmed death protein 1 (PD-1) developed by Shanghai Junshi Bioscience Co., Ltd. Toripalimab is able to bind to PD-1 and block the interaction with its ligands. The binding of toripalimab to PD-1 is mainly attributed to the heavy chain of the former and the FG loop of the latter. Toripalimab received a conditional approval in China for the treatment of melanoma (second-line) in December, 2018. It has also received approvals to treat nasopharyngeal carcinoma (first-line and third-line) and urothelial carcinoma (second-line) in 2021. Additionally, several orphan drug designations were granted to toripalimab by the US Food and Drug Administration. Toripalimab has exhibited primary anti-tumor effects in tumors such as melanoma, lung cancer, digestive tract tumors, hepatobiliary and pancreatic tumors, neuroendocrine neoplasms, nasopharyngeal carcinoma and urothelial carcinoma. It showed a satisfactory anti-tumor effect and long-term survival benefits in Chinese melanoma patients, while the combination of axitinib with toripalimab exhibited an impressive result in metastatic mucosal melanoma. As a checkpoint inhibitor, toripalimab was generally well-tolerated in the enrolled patients. Due to different study populations, comparisons could not be made directly between toripalimab and other drugs in most cases. Nevertheless, the introduction of toripalimab may offer a valuable choice for decision-making in the treatment of tumors in the future.
Highlights
T cells are important immune cells in the human body and express co-stimulating immune checkpoint proteins on their surface
In NCT02857166, patients were assigned to receive 0.3 mg/kg, 1 mg/kg, 3 mg/kg, 10 mg/kg or 240 mg toripalimab via intravenous infusion every 2 weeks; anti-drug antibodies were detected in one (33.3%) patient in the 0.3 mg/kg group, three (42.9%) patients in the 1 mg/kg group, and one (16.7%) patient in the 3 mg/kg group, but were not detected in the 10 mg/kg group or the 240 mg group [19]. These results indicate a low immunogenicity of toripalimab in the body
Due to the superior clinical benefit conferred by the combination plan, National Medical Product Administration (NMPA) have approved the indication of toripalimab plus GP as a first-line therapy in nasopharyngeal carcinoma (NPC) recently [7]
Summary
T cells are important immune cells in the human body and express co-stimulating immune checkpoint proteins on their surface. Toripalimab is the first monoclonal anti-PD-1 antibody approved by the China NMPA onto the market [10]. It consists of two heavy chains of 452 amino acids, two light chains of 219 amino acids, and includes an N-linked glycosylation site at N302 in each heavy chain. In in vitro flow cytometry assays, the inhibitory concentrations of toripalimab were 3.0 nmol/L and 3.1 nmol/L for PD-1/PD-L1 and PD-1/PD-L2, respectively [18]. In in vivo mouse models, by blocking the binding of PD-1 to PD-L1 or PDL2 using a protein-based enzyme-linked immunosorbent assay, the inhibitory concentrations of toripalimab were determined to be 0.8 nmol/L for PD-L1 and 1.3 nmol/L for PD-L2. Using a cellbased flow cytometry assay, the concentrations were 1.3 nmol/L and 3.7 nmol/L for PD-L1 and PD-L2, respectively [12]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
