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https://hdl.handle.net/123456789/1846| Τύπος: | Ανακοίνωση σε συνέδριο |
| Τίτλος: | Development of a novel approach of CAR technology towards immunotherapy of oral cancer |
| Συγγραφέας: | [EL] Μηλιώτου, Ανδρούλλα[EN] Miliotou, Androulla [EL] Ντέντη, Χαρίκλεια[EN] Ntenti, Charikleia [EL] Παππάς, Ιωάννης[EN] Pappas, Ioannis [EL] Παπαδοπούλου, Λευκοθέα[EN] Papadopoulou, Lefkothea |
| Ομιλητής: | [EL] Γεωργίου, Σοφία[EN] Georgiou, Sofia |
| Ημερομηνία: | 21/04/2022 |
| Περίληψη: | Chimeric Antigen Receptor (CAR) technology is a promising cell-based cancer immunotherapy, employing T-cells or Natural Killer (NK) cells, genetically engineered to express CAR receptors against tumor antigens. Oral cancer is highly resistant to conventional therapies and characterized by over-expression of ErbB proteins. ErbB receptors recognition via the ErbB ligand, T1E, fused to a CD28 plus CD3ζ endodomain, results in immune cells-mediated cytotoxicity in various types of cancer. Present work aims at development of CAR-NK-92 cells, through intracellular transduction of in vitro transcribed (IVT)-mRNAs, coding the CAR sequence and conjugated to a Protein Transduction Domain (PTD), via our novel, conjugation reaction (PCT/GR2020/000059). CAR- NK-92 cells aim to recognize, target and lyse human tongue squamous carcinoma cells (HSC-3). The CAR sequence was cloned into pGEM vector for in vitro transcription into mRNAs, which were then covalently conjugated to PTD. IVTmRNAs and PTD-IVT-mRNAs were incubated in serum-free medium for 1h at 37oC. PTD-IVT-mRNAs were significantly protected to RNase action. PTD-IVT-mRNAs were then incubated with NK-92 cells for different time intervals (2-72h). RT- PCR depicted that PTD-IVT-mRNAs successfully transduced into NK-92 cells since 2h of incubation, and thereafter. PTD-mediated IVT-mRNA transduction was not accompanied by cell death. Western blot analysis against the CD3ζ epitope showed that PTD-IVTmRNAs were expressed into the corresponding CAR molecules (35kDa) relatively rapid, persisted thereafter. Subcellular fractionation depicted that CAR molecules located to cellular membranes and cytoplasm, as well. Different co-incubation schemes, employing CAR-engineered NK-92 as the effectors and HSC-3 as the target cells, are now taking place. In conclusion, PTD Technology was successfully exploited for the rapid, efficient transduction and translation of the stable IVT-mRNA, encoding the CAR molecule into NK-92 cells. CAR-NK-92 cells have shown efficient cytotoxicity over HSC-3 cancer cells, leading to encouraging results for the application of our novel PTD-IVT- mRNA delivery platform for CAR immunotherapy. |
| Γλώσσα: | Αγγλικά |
| Τόπος δημοσίευσης: | Virtual Conference |
| Σελίδες: | 1 |
| Θεματική κατηγορία: | [EL] Φαρμακολογία και Φαρμακευτική[EN] Pharmacology and Pharmacy |
| Κάτοχος πνευματικών δικαιωμάτων: | © The Author(s) 2022 |
| Διατίθεται ανοιχτά στην τοποθεσία: | https://www.researchgate.net/publication/360614542_Development_of_a_novel_approach_of_CAR_Technology_towards_immunotherapy_of_oral_cancer |
| Όνομα εκδήλωσης: | Online International Conference on Pharmaceutics & Novel Drug Delivery Systems, Coalescence Research Group |
| Τοποθεσία εκδήλωσης: | Virtual Conference |
| Ημ/νία έναρξης εκδήλωσης: | 21/04/2022 |
| Ημ/νία λήξης εκδήλωσης: | 22/04/2022 |
| Εμφανίζεται στις συλλογές: | Ερευνητικές ομάδες |
Αρχεία σε αυτό το τεκμήριο:
| Αρχείο | Περιγραφή | Σελίδες | Μέγεθος | Μορφότυπος | Έκδοση | Άδεια | |
|---|---|---|---|---|---|---|---|
| Abstract Book_Pharmaceutics_2022.pdf | Book of Abstracts (Conference) | 990.94 kB | Adobe PDF | - |  | Δείτε/ανοίξτε |