Artikel ; 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 Band 73, Heft 3, Seite(n) 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. |
|---|---|
| Mesh-Begriff(e) | 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 |
| Chemische Substanzen | toripalimab (8JXN261VVA) ; Antibodies, Monoclonal ; B7-H1 Antigen ; Programmed Cell Death 1 Receptor ; Antibodies, Monoclonal, Humanized |
| Sprache | Englisch |
| Erscheinungsdatum | 2024-02-24 |
| Erscheinungsland | Germany |
| Dokumenttyp | 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 |
| Datenquelle | MEDical Literature Analysis and Retrieval System OnLINE |
Zusatzmaterialien
Kategorien
Verfügbar in ZB MED Köln/Königswinter
| Zs.A 1237: Hefte anzeigen | Standort: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG) |
Über subito bestellen
Dieser Service ist kostenpflichtig (siehe Lieferbedingungen von subito). Bestellungen, die einen Artikel nebst Supplementary Material umfassen, werden grundsätzlich wie mehrfache Bestellungen bearbeitet. Gebühren fallen in diesen Fällen für jede einzelne Bestellung an.