Article ; Online: Toripalimab, a therapeutic monoclonal anti-PD-1 antibody with high binding affinity to PD-1 and enhanced potency to activate human T cells.
Cancer immunology, immunotherapy : CII
2024 Volume 73, Issue 3, Page(s) 60
Abstract: Over the past decade, US Food and Drug Administration (FDA)-approved immune checkpoint inhibitors that target programmed death-1 (PD-1) have demonstrated significant clinical benefit particularly in patients with PD-L1 expressing tumors. Toripalimab is a ...
| Abstract | Over the past decade, US Food and Drug Administration (FDA)-approved immune checkpoint inhibitors that target programmed death-1 (PD-1) have demonstrated significant clinical benefit particularly in patients with PD-L1 expressing tumors. Toripalimab is a humanized anti-PD-1 antibody, approved by FDA for first-line treatment of nasopharyngeal carcinoma in combination with chemotherapy. In a post hoc analysis of phase 3 studies, toripalimab in combination with chemotherapy improved overall survival irrespective of PD-L1 status in nasopharyngeal carcinoma (JUPITER-02), advanced non-small cell lung cancer (CHOICE-01) and advanced esophageal squamous cell carcinoma (JUPITER-06). On further characterization, we determined that toripalimab is molecularly and functionally differentiated from pembrolizumab, an anti-PD-1 mAb approved previously for treating a wide spectrum of tumors. Toripalimab, which binds the FG loop of PD-1, has 12-fold higher binding affinity to PD-1 than pembrolizumab and promotes significantly more Th1- and myeloid-derived inflammatory cytokine responses in healthy human PBMCs in vitro. In an ex vivo system employing dissociated tumor cells from treatment naïve non-small cell lung cancer patients, toripalimab induced several unique genes in IFN-γ and immune cell pathways, showed different kinetics of activation and significantly enhanced IFN-γ signature. Additionally, binding of toripalimab to PD-1 induced lower levels of SHP1 and SHP2 recruitment, the negative regulators of T cell activation, in Jurkat T cells ectopically expressing PD-1. Taken together, these data demonstrate that toripalimab is a potent anti-PD-1 antibody with high affinity PD-1 binding, strong functional attributes and demonstrated clinical activity that encourage its continued clinical investigation in several types of cancer. |
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| MeSH term(s) | Humans ; Antibodies, Monoclonal/therapeutic use ; Carcinoma, Non-Small-Cell Lung/pathology ; B7-H1 Antigen ; Programmed Cell Death 1 Receptor ; Lung Neoplasms/drug therapy ; Nasopharyngeal Carcinoma ; Esophageal Neoplasms/drug therapy ; Esophageal Squamous Cell Carcinoma/drug therapy ; Nasopharyngeal Neoplasms ; T-Lymphocytes/pathology ; Antibodies, Monoclonal, Humanized |
| Chemical Substances | toripalimab (8JXN261VVA) ; Antibodies, Monoclonal ; B7-H1 Antigen ; Programmed Cell Death 1 Receptor ; Antibodies, Monoclonal, Humanized |
| Language | English |
| Publishing date | 2024-02-24 |
| Publishing country | Germany |
| Document type | Journal Article |
| ZDB-ID | 195342-4 |
| ISSN | 1432-0851 ; 0340-7004 |
| ISSN (online) | 1432-0851 |
| ISSN | 0340-7004 |
| DOI | 10.1007/s00262-024-03635-3 |
| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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